(1S,3R,5R)-PIM447 (dihydrochloride) an PIM inhibitor extracted from patent US 20100056576 A1, compound example 72, has IC50 values of 0.095 μM for Pim1, 0.522 μM for Pim2 and 0.369 μM for Pim3.

A novel selective STAT3 inhibitor with IC50 of 4.2 uM, does not inhibit STAT1, STAT5, or NFkB signaling pathways (IC50>50 uM).

A orally bioavailable small-molecule STAT3 inhibitor.

A platinum-containing compound that disrupts STAT3 signaling, inhibits cell growth and induces apoptosis in STAT3-activated cancer cells.

A potent and highly selective JAK3 inhibitor with IC50 of 0.15 nM.

A potent, highly specific JAK3 inhibitor with IC50 of 4 nM.

AG-490 (Tyrphostin B42) is an inhibitor of EGFR, ErbB2 and JAK2 with IC50 of 0.1 μM, 13.5 μM, and ~10 μM, respectively.

AS 602801(Bentamapimod) is a novel, orally active inhibitor of JNK.

AS1517499 is a potent STAT6 inhibitor with IC50 of 21 nM.

AZ 960 is a novel ATP competitive JAK2 inhibitor with IC50 and Ki of <3 nM and 0.45 nM, 3-fold selectivity of AZ960 for JAK2 over JAK3.

AZD1208 is orally available, small molecule inhibitor of PIM kinases with potential antineoplastic activity.

AZD1480 is a novel ATP-competitive JAK2 inhibitor with IC50 of 0.26 nM, selectivity against JAK3 and Tyk2, and to a smaller extent against JAK1. Phase 1/2.

Baricitinib is a selective JAK1 and JAK2 inhibitor with IC50 of 5.9 nM and 5.7 nM, ~70 and ~10-fold selective versus JAK3 and Tyk2, no inhibition to c-Met and Chk2,showed potent activity against COVID-19(SARS-COV-2).

Baricitinib phosphate(INCB 028050; LY 3009104) is a selective JAK1 and JAK2 inhibitor with IC50 of 5.9 nM and 5.7 nM, ~70 and ~10-fold selective versus JAK3 and Tyk2, no inhibition to c-Met and Chk2,showed potent activity against COVID-19(SARS-COV-2).

BMS-911543 is a potent and selective inhibitor of JAK2 with IC50 of 1.1 nM, approximately 350-, 75- and 65-fold selective to JAK1, JAK3 and TYK2, respectively.

BP-1-102 is a potent, orally bioavailable and selective STAT3 inhibitor.

BTZ043 is a inhibitor of decaprenyl-phosphoribose-epimerase (DprE1), It can display nanomolar bactericidal activity against Mycobacterium tuberculosis in vitro.

BTZ043 racemate is a decaprenylphosphoryl-β-D-ribose 2-epimerase (DprE1) inhibitor acting as a new antimycobacterial agent that kill Mycobacterium tuberculosis.

C188-9 is a potent inhibitor of STAT3 that binds to STAT3 with high affinity (KD=4.7±0.4 nM). C188-9 is well tolerated in mice, shows good oral bioavailability, and is concentrated in tumors.

CEP33779(< 3 μM) inhibits phosphorylation of downstream target signal transducer and activator of transcription 5(pSTAT5) of JAK2 in a concentration dependent manner in HEL92 cells.

Cerdulatinib(PRT-062070; PRT2070) is an novel oral dual Syk/JAK inhibitor.

CHZ868 is a type II JAK2 inhibitor with an IC50 of 0.17 μM in EPOR JAK2 WT Ba/F3 cell.

CX-6258 is a potent, orally efficacious Pim 1/2/3 kinase(IC50=5 nM/25 nM/16 nM) inhibitor with excellent biochemical potency and kinase selectivity.

CYT387 is an ATP-competitive inhibitor of JAK1 and JAK2 with IC50 of 11 nM and 18 nM, respectively.

Debio 0617B has been developed as a first-in-class kinase inhibitor with a unique profile targeting phospho-STAT3 (pSTAT3) and/or pSTAT5 in tumors through combined inhibition of JAK, SRC, ABL, and class III/V receptor tyrosine kinases (RTK).

Decernotinib(VX-509; VRT-831509) is a potent and selective Janus kinase 3 (JAK3) inhibitor with Ki of 2.5 nM; IC50 is 50-170 nM in cellular assays.

Delgocitinib (JTE-052, LEO 124249) is a potent, selective, orally active, pan-JAK inhibitor with IC50 of 2.8, 2.6, 13 and 58 nM for JAK1,2,3 and Tyk2, respectively.

FLLK31 is a potent and selective inhibitor of the STAT3 signaling pathway.

FLLL32, a novel curcumin analogue, is a potent STAT3 inhibitor.

FM-381 is a JAK3 specific reversible covalent inhibitor with IC50 of 127 pM for JAK3 and demonstrates 400-, 2,700- and 3,600-fold selectivity over JAK1, JAK2, and TYK2, respectively.

GLPG0634 (analog) is a pan JAK inhibitor with IC50s of 50-200 nM for JAK1/JAK2/JAK3; more information can be found in the reference patents.

GPLG0634 is a novel inhibitor of JAK1 and JAK2 with IC50 of 10nM and 28nM respectively.

Hispidulin is a natural flavone with a broad spectrum of biological activities. Hispidulin is a Pim-1 inhibitor with an IC50 of 2.71 μM.

HJC0152 is a signal transducer and activator of transcription 3 (STAT3) inhibitor with remarkably improved aqueous solubility.

INCB053914 (INCB-053914) is a novel potent, and selective ATP-competitive, pan-PIM kinase inhibitor with IC50 of 0.24/30.0/0.12 nM for PIM1/2/3, respectively.

inS3-54A18 is a potent STAT3 inhibitor, with anti-cancer properties.

Itacitinib is a potent and selective inhibitor of JAK1, with >20-fold selectivity for JAK1 over JAK2 and >100-fold over JAK3 and TYK2; Itacitinib is used in the research of myelofibrosis.

JAK2 inhibitor G5-7 is a small molecule, allosteric JAK2 inhibitor that selectively inhibits JAK2-mediated phosphorylation and activation of EGFR and STAT3 by binding to JAK2.

Janex 1 selectively inhibits the tyrosine kinase activity of JAK3 with an IC50 value of 78 µM without affecting the enzymatic activity of JAK1, JAK2, or other protein tyrosine kinases (IC50 ≥350 µM).

LY2784544 is a potent JAK2 inhibitor with IC50 of 3 nM, effective in JAK2V617F, 8- and 20-fold selective versus JAK1 and JAK3. Phase 2.

Merck 5 is a potent and reversible ATP-competitive inhibitor of the JAK kinases (JAK1, JAK2, JAK3, and Tyk2). It also blocks IL2 and IL4 dependent proliferation of CTLL cells and inhibits the phosphorylation of STAT5.

Napabucasin (BBI608) is an orally-administered small molecule which can block cancer stem cell (CSC) self-renewal and induces cell death in CSCs as well as non-stem cancer cells.

NSC 31205 is a PIM2/1 inhibitor.

NVP-BSK805 is a potent and selective ATP-competitive JAK2 inhibitor with IC50 of 0.5 nM; >20-fold selectivity towards JAK1, JAK3 and TYK2.

Pacritinib (SB1518) is a potent and selective JAK2 (IC50 = 23 and 19 nM for JAK2WT and JAK2V617F, respectively) and FLT3 (IC(50) = 22 nM) inhibitor with selectivity against JAK1 and JAK3 (IC50= 1280 and 520 nM, respectively).

Peficitinib(ASP015K,JNJ-54781532) is a novel potent JAK inhibitor, which demonstrated potent efficacy in adjuvant-induced arthritis model in rats.

PF-06263276 (PF06263276, PF 6263276) is a potent, selective pan JAK inhibitor with IC50 of 2.2, 23.1, 59.9 and 29.7 nM for JAK1, JAK2, JAK3, and TYK2, respectively.

PF-06651600 is a potent JAK3-selective inhibitor with an IC50 of 33.1 nM.

PF-06700841 is an inhibitor of JAK1 and TYK2 kinases. PF-06700841 has been investigated for the treatment of psoriasis and lupus.

PF-06700841 is an inhibitor of JAK1 and TYK2 kinases. PF-06700841 has been investigated for the treatment of psoriasis and lupus.

PIM/AKK1-IN-1 is a potent multi-kinase inhibitor with Kd values of 35 nM/53 nM/75 nM/380 nM for Pim1/AKK1/MST2/LKB1 respectively; also inhibits MPSK1 and TNIK.

PIM447 is novel pan-PIM kinase inhibitor, including Moloney Murine Leukemia (PIM) 1, 2, and 3 Kinase.

Pimobendan is a selective inhibitor of PDE3 with IC50 of 0.32 μM.

Piperlongumine induces cell death and increases the level of reactive oxygen species (ROS) in cancer cells with both wild-type and normal p53.

Potent Pim-1 kinase inhibitor (Ki = 91 nM).

Ruxolitinib is a potent ATP mimetic that inhibits both JAK1 and JAK2 with IC50 values of 2.7 and 4.5 nM, respectively and is relatively less selective for JAK3 (IC50 = 322 nM).

Ruxolitinib Phosphate is a potent and selective Janus kinase (JAK1, IC50 = 5.9 nM and JAK2, IC50 = 5.7 nM) inhibitor.

SAR-20347 is an inhibitor of TYK2, JAK1, JAK2 and JAK3 with IC50s of 0.6, 23, 26 and 41 nM, respectively.

SGI-1776 is a novel ATP competitive inhibitor of Pim1 with IC50 of 7 nM; 50- and 10-fold selective versus Pim2 and Pim3, also potent to Flt3 and haspin.

SH-4-54 is a potent STAT inhibitor with KD of 300 nM and 464 nM for STAT3 and STAT5, respectively.

SH5-07 is a hydroxamic acid based Stat3 inhibitor with an IC50 of 3.9±0.6 μM in in vitro assay.

SMI-16a is a selective Pim kinase inhibitor with IC50 values of 0.15, 0.02 and 48 μM for Pim1, Pim2 and PC3 cells, respectively.

SMI-4a is a potent inhibitor of Pim1 with IC50 of 17 nM, modest potent to Pim-2, does not significantly inhibit other serine/threonine- or tyrosine-kinases.

Solcitinib, also known as GSK2586184 or GLPG0778, is a Janus kinase 1 (JAK1) inhibitor.

Stat5 Inhibitor is a cell permeable nonpetidic nicotinoyl hydrazone which suppresses Stat5 via binding to the SH2 domain.

TCS PIM-1 1 is a potent and selective ATP-competitive Pim-1 kianse inhibitor with IC50 of 50 nM, displays good selectivity over Pim-2 and MEK1/MEK2(IC50s >20,000 nM).

TG101209 is a selective JAK2 inhibitor with IC50 of 6 nM, less potent to Flt3 and RET with IC50 of 25 nM and 17 nM, ~30-fold selective for JAK2 than JAK3, sensitive to JAK2V617F and MPLW515L/K mutations; TG101209 inhibit BRD4 activity with IC50 of 130 nM.

TG-101348 (SAR302503) is a selective inhibitor of JAK2 with IC50 of 3 nM, 35- and 334-fold more selective for JAK2 versus JAK1 and JAK3, TG-101348 also inhibit BRD4 with IC50 of 340 nM.

TG-46 is an inhibitor of JAK2, FLT3, RET, JAK3 with IC50 values of 6nM, 25nM, 17nM, 169nM respectively.

TG-89 is a JAK inhibitor. It has IC50 values of 6, 25, 17 and 169 nM against JAK2, FLT3, RET and JAK3 respectively.

Tofacitinib is a novel inhibitor of JAK3 with IC50 of 1 nM, 20- to 100-fold less potent versus JAK2 and JAK1. Phase 3.

Tofacitinib is a novel inhibitor of JAK3 with IC50 of 1 nM, 20- to 100-fold less potent versus JAK2 and JAK1. Phase 3.

TP-3654 is a small molecule pan-Pim (PIM) kinase inhibitor.

Upadacitinib (ABT-494) is a potent and selective Janus kinase (JAK) 1 inhibitor being developed for the treatment of several autoimmune disorders with an IC50 of 43 nM.

WHI-P154 is a potent JAK3 inhibitor with IC50 of 1.8 μM, no activity against JAK1 or JAK2, also inhibits EGFR, Src, Abl, VEGFR and MAPK, prevents Stat3, but not Stat5 phosphorylation.

WHI-P258 is a negative control for JAK3 inhibitors.

WHI-P97 is a rationally designed potent inhibitor of JAK-3.

XL019 is an orally bioavailable inhibitor of Janus-associated kinase 2 (JAK2) with potential antineoplastic activity.

YLT-11 is a novel and specific PLK4 inhibitor with IC50 of 22 nM and Kd of 5.2 nM.

Z3(NSC 42834), a novel specific inhibitor of Jak2, inhibits Jak2-V617F and Jak2-WT autophosphorylation in a dose-dependent manner but was not cytotoxic to cells at concentrations that inhibited kinase activity.

ZM 39923 is an inhibitor of JAK3 (IC50 = 79 nM) that less potently inhibits epidermal growth factor receptor, JAK1, and cyclin-dependent kinase 4 (IC50s = 2.4, 40, and 10 µM, respectively).

S-Ruxolitinib is the chirality of INCB018424, which is the first potent, selective, JAK1/2 inhibitor to enter the clinic with IC50 of 3.3 nM/2.8 nM, >130-fold selectivity for JAK1/2 versus JAK3. Phase 3.

Fedratinib hydrochloride hydrate (TG-101348 hydrochloride hydrate) is a potent, selective, ATP-competitive and orally active JAK2 inhibitor with IC50s of 3 nM for both JAK2 and JAK2V617F kinase. Fedratinib hydrochloride hydrate shows 35- and 334-fold selectivity over JAK1 and JAK3, respectively. Fedratinib hydrochloride hydrate induces cancer cell apoptosis and has the potential for myeloproliferative disorders research.

(R)-Lisofylline ((R)-Lisophylline) is a (R)-enantiomer of the metabolite of Pentoxifylline with anti-inflammatory properties. (R)-Lisofylline is a lysophosphatidic acid acyltransferase inhibitor with an IC50 of 0.6 μM and interrupts IL-12 signaling-mediated STAT4 activation. (R)-Lisofylline has the potential for type 1 diabetes, autoimmune disorders research.

JAK-IN-5 hydrochloride is an inhibitor of JAK extracted from patent US20170121327A1, compound example 283.

SHR0302 is a potent and orally active all members of the JAK family inhibitor, particularly JAK1. The selectivity of SHR0302 for JAK1 is >10-fold for JAK2, 77-fold for JAK3, 420-fold for Tyk2. SHR0302 inhibits JAK1-STAT3 phosphorylation and induces the apoptosis of hepatic stellate cells. SHR0302 has anti-proliferative and anti-inflammatory effects.

FM-479 is the negative control of FM-381 and has no activity on JAK3 or other kinases.

BD750, an effective immunosuppressant and a JAK3/STAT5 inhibitor, inhibits IL-2-induced JAK3/STAT5-dependent T cell proliferation, with IC50 values of 1.5 μM and 1.1 μM in mouse and human T cells, respectively.

ZM 449829 is a potent, selective and ATP competitive inhibitor of JAK3, with a pIC50 of 6.8. ZM 449829 will be useful pharmacological tools for the investigation of the JAK3.

JAK2-IN-6, a multiple-substituted aminothiazole derivative, is a potent and selective JAK2 inhibitor with an IC50 of 22.86 μg/mL. JAK2-IN-6 shows no activity against JAK1 and JAK3. JAK2-IN-6 has anti-proliferative effect against cancer cells.

Coumermycin A1 is a JAK2 signal activator. Coumermycin A1 inhibits DNA Gyrase which thereby inhibits cell division in bacteria.

Angoline is a potent and selective IL6/STAT3 signaling pathway inhibitor with an IC50 of 11.56 μM. Angoline inhibits STAT3 phosphorylation and its target gene expression, and inhibits cancer cell proliferation.

Angoline hydrochloride is a potent and selective IL6/STAT3 signaling pathway inhibitor with an IC50 of 11.56 μM. Angoline hydrochloride inhibits STAT3 phosphorylation and its target gene expression, and inhibits cancer cell proliferation.

APTSTAT3-9R, a specific STAT3-binding peptide, inhibits STAT3 activation and downstream signaling by specifically blocking STAT3 phosphorylation. APTSTAT3-9R exerts antiproliferative effects and antitumor activity.

JAK2-IN-7 is a selective JAK2 with IC50s of 3, 11.7, and 41 nM for JAK2, SET-2, and Ba/F3V617F cells. JAK2-IN-7 possesses >14-fold selectivity over JAK1, JAK3, FLT3. JAK2-IN-7 stimulates cell cycle arrest in the G0/G1 phase and induces tumor cellapoptosis. Antitumor activities.

(3S,4S)-Tofacitinib is the less active S-enantiomer of Tofacitinib. Tofacitinib inhibits JAK3 with IC50 of 1 nM.

PIM1-IN-1 is a potent and highly selective PIM1/3 inhibitor, with IC50s of 7, 5530 and 70 nM for PIM1, PIM2, and PIM3, respectively, inhibits the phosphorylation of BAD, a downstream target of PIM, with an EC50 of 262 nM. PIM1-IN-1 shows no obvious effect on FLT3 or hERG binding. Antiproliferative and anti-cancer activity.

JAK2/FLT3-IN-1 is a potent and orally active dual JAK2/FLT3 inhibitor with IC50 values of 0.7 nM, 4 nM, 26 nM and 39 nM for JAK2, FLT3, JAK1 and JAK3, respectively. JAK2/FLT3-IN-1 has anti-cancer activity.

AS1810722 is an orally active and potent STAT6 inhibitor with an IC50 of 1.9 nM. AS1810722 shows a good profile of CYP3A4 inhibition. AS1810722 has the potential for allergic diseases such as asthma and atopic diseases.

(E/Z)-AG490 ((E/Z)-Tyrphostin AG490) is a racemic compound of (E)-AG490 and (Z)-AG490 isomers. (E)-AG490 is a tyrosine kinase inhibitor that inhibits EGFR, Stat-3 and JAK2/3.

R8-T198wt is a cell-permeable carboxyl-terminal p27Kip1 peptide exhibits anti-tumor activity by inhibiting Pim-1 kinase.

Colivelin is a brain penetrant neuroprotective peptide and a potent activator of STAT3, suppresses neuronal death by activating STAT3 in vitro. Colivelin exhibits long-term beneficial effects against neurotoxicity, Aβ deposition, neuronal apoptosis, and synaptic plasticity deficits in neurodegenerative disease. Colivelin has the potential for the treatment of alzheimer's disease and ischemic brain injury

CMD178 is a lead peptide that consistently reduced the expression of Foxp3 and STAT5 induced by IL-2/s IL-2Rα signaling. CMD178 also is an inhibitor of STAT5 and inhibit Treg cell development.

Deuruxolitinib (CTP-543), a deuterated Ruxolitinib, modulates the activity of JAK1/JAK2. Deuruxolitinib can be used for the research hair loss disorders (from patent WO2017192905A1, compound I).

JAK2/FLT3-IN-1 (TFA) is a potent and orally active dual JAK2/FLT3 inhibitor with IC50 values of 0.7 nM, 4 nM, 26 nM and 39 nM for JAK2, FLT3, JAK1 and JAK3, respectively. JAK2/FLT3-IN-1 (TFA) has anti-cancer activity.

Nezulcitinib (TD-0903) is an inhaled and lung-selective pan-Janus kinase (JAK) inhibitor. Nezulcitinib can be used for the research of COVID-19 associated acute lung injury and impaired oxygenation.

Ilunocitinib (compound 27) is a JAK inhibitor (extracted from patent WO2009114512A1).

Fosifidancitinib is a potent and selective inhibitor of JAK kinases 1/3. Fociatinib is used in studies of allergies, asthma and autoimmune diseases.

Itacnosertib (TP-0184) is both inhibitor to JAK2, ACVR1 (ALK2) and ALK5 as described in WO2014151871.

Lorpucitinib is a Gut-Restricted JAK Inhibitor for the research of Inflammatory Bowel Disease.

Ifidancitinib is a potent and selective inhibitor of JAK kinases 1/3. Ifidancitinib can be used in studies of allergies, asthma and autoimmune diseases.

JAK1-IN-8, a potent JAK1 inhibitor (IC50<500 nM), compound 28, extracted from patent WO2016119700A1.

MNK/PIM-IN-1 represents an innovative dual MNK/PIM inhibitor with a good pharmacokinetic profile.

Ten01 has 5.0 nM activity against JAK1 kinase.

JAK-IN-14 is a potent and selective JAK1 inhibitor, with an IC50 of <5 μM. JAK-IN-14 is >8-fold more selective for JAK1 than JAK2 and JAK3 (Patent WO2016119700A1, compound 16).

JAK1/TYK2-IN-1 is a dual inhibitor of TYK2 and JAK1 (IC50 = 29 and 41 nM respectively).

Povorcitinib is a potent and selective inhibitor of JAK1. Povorcitinib has the potential for the research of disease selected from cutaneous lupus erythematosus (CLE) and Lichen planus (LP) (extracted from patent WO2021076124A1).

PIM-IN-1 is a pan-PIM kinase inhibitor (KG-1, EC50 = 61 nM; pS6, EC50 = 71 nM).

GDC-4379 is a JAK1 inhibitor that can be used for the research of asthma.

JAK2/TYK2-IN-2 is a potent and selective TYK2 inhibitor with IC50 values of 9 and 157 nM for TYK2 and JAK2, respectively. JAK2/TYK2-IN-2 has anti-inflammatory activity.

JAK1/TYK2-IN-3 is a potent, selective and orally active dual TYK2/JAK1 inhibitor with IC50 values of 6 and 37 nM, respectively. JAK1/TYK2-IN-3 also shows selectively relative to JAK2 (IC50=140 nM) and JAK3 (IC50=362 nM). JAK1/TYK2-IN-3 shows anti-inflammatory effect by regulating the expression of related TYK2/JAK1-regulated genes, as well as the formation of Th1, Th2, and Th17 cells.

JAK-IN-19 is a potent JAK inhibitor (PBMC IFNγ pIC50=7.2 and HLF Eotaxin pIC50=7.7). JAK-IN-19 has good retentive properties in the lung via mitigating being metabolized by Aldehyde Oxidase (AO), with diminished VEGFR2 selectivity (VEGFR2 pIC50=7.0, Aurora B pIC50=5.8).

Tofacitinib Prodrug-1 is an effective and oral active prodrug to mitigate the systemic adverse effects of Tofacitinib. Tofacitinib Prodrug-1 can effectively attenuate the oxazolone-induced colitis in mice model with low toxicity. Tofacitinib Prodrug-1 is a potential drug candidate for the treatment of ulcerative colitis.

Danvatirsen is an antisense oligonucleotide targeting STAT3 with potential antitumor activity. Danvatirsen binds to STAT3 mRNA, thereby inhibiting translation of the transcript. Suppression of STAT3 expression induces tumor cell apoptosis and decreases tumor cell growth.

5,15-Diphenylporphyrin (5,15-DPP) is a selective STAT3-SH2 antagonist (IC50s of 0.28 µM and 10 µM for STAT3 and STAT1, respectively).

STAT3-IN-7, an aryl sulfonamido azetidine compound, is an orally active STAT3 inhibitor. STAT3-IN-7 has anticancer activities (WO2021016333A1, H182).

2-NP is a selective enhancer of STAT1 transcription. 2-NP can enhance the ability of IFN-γ to inhibit the proliferation of human breast cancer and fibrosarcoma cells.

Napabucasin (BBI-608) is a potent small-molecule inhibitor of STAT3 that has a broad spectrum of activity against stemness-high cancer cells (IC50=0.5-1.5 uM).

GDC-0339 (GDC0339) is a novel small molecule pan-Pim kinase inhibitor that was discovered as a potential treatment for multiple myeloma.

Flonoltinib maleate is a potent, highly selective, dual JAK2/FLT3 inhibitor with IC50 of 0.8, 1.4, and 15 nM for JAK2, JAK2V617F, and FLT3, respectively.

A novel small molecule SH2 domain-targeting STAT3 inhibitor with IC50/Kd of 7.3/5 nM; does not bind to the S636A, V637A, and E638A SH2D mutants; effectively inhibits STAT3 phosphorylation (pTyr705 and pSer727) and cancer cell proliferation, impairs mitochondrial function; shows potent activity tumor xenografts in mice; orally bioactive.

A novel STAT3 inhibitor (IC50=18.7 nM; Kd=10 nM) that strongly inhibits STAT3 and STAT5 phosphorylation without upstream kinase inhibition; induces significant growth inhibition in various hematopoietic malignant cells, particularly effective against multiple myeloma, Burkitt lymphoma and leukemia harboring BCR-ABL, FLT3/ITD and JAK2 V617F, oncokinases with their oncogenicities dependent on STAT3/5.

AZD4604 (AZD-4604) is a potent, selective Janus-associated kinase 1 (JAK1) inhibitor with anti-inflammatory effect.

BMS-986202 (BMS 986202) is potent, selective Tyk2 inhibitor that binds to Tyk2 JH2 domain with IC50 of 0.19 nM, Ki of 0.02 nM, >10,000-fold over 273 kinases and pseudokinases; BMS-986202 demonstrated cellular activity (IL-23 IC50=12 nM) in IL-23 stimulated reporter assay (in Kit225 T cells). BMS-986202 also binds Jak1 JH2 with an IC50 of 7.8 nM, but this enzymatic binding did not lead to any functional activities, as BMS-986202 displayed an activity (IC50) of greater than 12.5 μM in the IL-2 stimulated Jak1/3-dependent cellular assay. BMS-986202 showed in vivo efficacy in mouse models of IL-23-driven acanthosis, anti-CD40-induced colitis, and spontaneous lupus.

JP-11646 is a novel potent, selective, non-ATP competitive Pim2 inhibitor with IC50 of 0.5/1/24 nM for Pim2/3/1, respectively; shows less potency for other kinases in a kinase selectivity panel; exhibits 4-760-fold greater suppression of MM proliferation and viability than ATP-competitive PIM inhibitors; significant reduces tumor burden and increases median survival in xenogeneic myeloma murine models.

LAS194046 (LAS-194046) is a potent, selective pan-JAK inhibitor with IC50 of 5.46/0.4/ 2.07 nM against JAK1/2/3, less potent in TYK2 activity (IC50=21.8 nM).LAS194046 is effective at blocking cytokine signaling depending on JAK1/JAK3, both in lymphocytes and monocytes, and JAK2/JAK2 in monocytes with IC50 of 16 nM, 26 nM and 37 nM, respectively.LAS194046 reduces allergen-induced airway inflammation, late asthmatic response, and phosphor-STAT activation in the rat OVA model.

NDI-031407 (NDI 031407) is a novel potent, selective TYK2 inhibitor with IC50 of 0.21 nM in radiometric assays, 20 fold selectivity over JAK3 (4.2 nM), 147 fold for JAK2 (31 nM), and 220 fold for JAK1 (46 nM).NDI-031407 has high potency in cell line and primary cell assays for TYK2-dependent cytokines (IL-12, IC50=118 nM) over TYK2-independent cytokines (GM-CSF).NDI-031407 blocks IL-23–induced STAT3 phosphorylation and IL-17A production in human CD4+ T cells.NDI-031407 inhibits disease progression in the SKG model of Spondyloarthritis (SpA).NDI-031407 suppresses systemic IL-23–induced type 3 immunity in vivo.

OX01401 (OX-01401, OX1401) is a potent, selective and cell active inhibitor of the PIM kinase family (PIM1 IC50=15.1 nM).OX01401 inhibited proliferation of two PIM-expressing leukaemic cancer cell lines, MV4-11 (IC50=0.5 uM) and PC3 cell (IC50=1.1 uM), and to reduced intracellular phosphorylated 4EBP1 protein in a concentration dependent manner.

SI-109 (SI 109) is a selective, high-affinity and cell-permeable STAT3 SH2 domain inhibitor with Ki of 9 nM, component of STAT3 degrader SD-36 (PROTAC).

SS-4 (STAT3 inhibitor SS-4) is a highly selective small molecule inhibitor of STAT3 tyrosine phosphorylation that potently inhibits GBM tumorigenesis in vitro and in vivo.SS-4 strongly and selectively inhibits STAT3 Y-705 phosphorylation in MT330 and LN229 GBM cells and inhibits their proliferation and inducs apoptosis with an IC50 of 100 nM.SS-4 increases the expression of STAT3 repressed genes, while decreasing the expression of STAT3 promoted genes.SS-4 markedly reduces the growth of GBM intracranial tumor xenografts.

Stafia-1 prodrug is the cell‐permeable prodrug of Stafia-1, suitable for cell based assays, inhibits tyrosine phosphorylation of STAT5a with selectivity over STAT5b in cultured human leukemia cells.

Stat3 inhibitor H182 is a potent, selective STAT3 inhibitor, inhibits Stat3 DNA-binding activity with IC50 of 0.66 uM.Stat3 inhibitor H182 shows selective inhibition of Stat3:Stat3 DNA-binding activity, over the inhibition of Stat1:Stat3 (IC50 of 3.4-8.3 μM), with far lower potencies against Stat1:Stat1 (IC50 > 15.8 uM) and Stat5:Stat5 activities (IC50 >19.1 uM).Stat3 inhibitor H182 irreversibly and covalently binds (KD=1.97 uM, ITC) to Stat3 key residues Cys426 and Cys468.Stat3 inhibitor H182 inhibits constitutive and ligand-induced Stat3 activation (pY705Stat3) and blocks Stat3 nuclear accumulation with no change in Stat3 protein levels in breast cancer cells, with little or no effects on pS727Stat3, Stat1, JAK2, EGFR, Shc, Erk1/2, Src, or Akt induction.Stat3 inhibitor H182 inhibited anchorage-dependent and independent growth (MDA-MB-231, IC50=1 uM), induced apoptosis, and suppressed Stat3 target gene expression in TNBC cells harboring constitutively-active Stat3.Stat3 inhibitor H182 inhibited growth of breast tumors in mice, enhanced response to radiation and prolonged survival.

STAT3 inhibitor N4 is a small molecule capable of inhibiting the STAT3 SH2 domain with IC50 of 0.57 uM, SPR KD of 1.04 uM, inhibits STAT3 dimerization and transcription in vitro and suppresses pancreatic cancer in vivo.N4 suppresses STAT3 activation in pancreatic cancer cells, suppresses pancreatic cancer cell growth, migration, and induces apoptosis.N4 (20 mg/kg, i.p.) suppresses pancreatic cancer growth, exhibits potent anti-metastatic activity in a pancreatic cancer liver metastasis mouse model, and prolongs survival of tumor-bearing mice.

TD-1473 (Izencitinib, TD1473, JNJ 8398) is a potent, selective, oral gut-selective pan-JAK inhibitor with pKi of 10.0/10.0/8.8/9.5 for human recombinant JAK1, JAK2, JAK3 and TYK2.TD-1473 inhibited cytokine-induced phosphorylation of STAT1 in mouse primary colonic epithelial cells with pIC50 values for inhibition against IL-6, IFNα and IFNγ were 7.3, 6.8 and 7.0.TD-1473 demonstrated JAK inhibitory activity in ex vivo mouse colon and human IBD patient colonic tissue. TD-1473 (Izencitinib) is under development for the treatment of ulcerative colitis.

Humanin (human) (1-24-Protein humanin (human)), a small mitochondrial-derived cytoprotective polypeptide encoded by mtDNA, exhibits protective effects in several cell types against cellular stress conditions and apoptosis through regulating various signaling mechanisms, such as JAK/STAT pathway and interaction of BCL-2 family of protein.

SD-1008 is a potent JAK inhibitor. SD-1008 inhibits tyrosyl phosphorylation of STAT3, JAK2 and Src. SD-1008 also reduces STAT3-dependent luciferase activity. SD-1008 enhances apoptosis induced by Paclitaxel in ovarian cancer cells via directly blocking the JAK-STAT3 signaling pathway.

Prohibitin ligand 1 (Compound 22i), a cardioprotectant prohibitin ligand, induces a phosphorylation of the pro-survival factor STAT3. Prohibitin ligand 1 exhibits in vitro cardioprotectant activities at nanomolar concentrations.

MNK8 is a potent STAT3 (signal transducer and activator of transcription 3) inhibitor. MNK8 inhibits STAT3 activation and reduced its DNA binding ability. MNK8 shows good growth inhibition against hepatocellular carcinoma (HCC) cells. MNK8 induces apoptosis in HCC cells. MNK8 reduces prosurvival proteins expression and migration/invasion of HCC cells.

Peficitinib (ASP015K) hydrobromide is an orally active JAK inhibitor, with IC50s of 3.9, 5.0, 0.7 and 4.8 nM for JAK1, JAK2, JAK3 and Tyk2, respectively.

Quercetagetin (6-Hydroxyquercetin), a flavonoid, is a moderately potent and selective, cell-permeable Pim-1 kinase inhibitor with IC50 of 0.34 μM.

IST5-002, a potent Stat5a/b inhibitor, selectively inhibits transcriptional activity of Stat5a/b (IC50s: 1.5 μM for Stat5a, 3.5 μM for Stat5b). IST5-002 inducs cell apoptotic and death of prostate cancer cells and chronic myeloid leukemia (CML) cells. IST5-002 can be used in the research of prostate cancer and chronic myeloid leukemia (CML).

SJ1008030 (compound 8) is a JAK2 PROTAC which selectively degrades JAK2. SJ1008030 inhibits MHH–CALL-4 cells with an EC50 of 5.4 nM and an IC50 of 32.09 nM. SJ1008030 can be used for the research of leukemia.

VVD-118313 (compound 5a) is a potent, selective JAK1 inhibitor. VVD-118313 targets an isoform-restricted allosteric cysteine to block JAK1-dependent trans-phosphorylation and cytokine signaling. VVD-118313 can be used for research of cancer.

Peficitinib (ASP015K) hydrochloride is an orally active JAK inhibitor, with IC50s of 3.9, 5.0, 0.7 and 4.8 nM for JAK1, JAK2, JAK3 and Tyk2, respectively.

(S)-PM-43I is a potent STAT6 inhibitor and can reduce STAT6 phosphorylation level. (S)-PM-43I can be used in allergic lung disease, allergic rhinitis, chronic pulmonary obstructive disease and cancer research[1].

PM-81I is a potent STAT6 inhibitor (targeting the SH2 structural domain) that effectively reduces STAT6 phosphorylation levels. PM-81I can be used in studies of allergic lung disease, allergic rhinitis, chronic obstructive pulmonary disease or cancer[1].

NDI034858 is a TYK2 inhibitor, target TYK2 JH2 domain with binding constant Kd of <200 pM.

HP590 is an orally active, novel and potent STAT3 inhibitor (STAT3 luciferase activity: IC50=27.8 nM; ATP inhibition: IC50=24.7 nM). HP590 shows anti-proliferative activity to gastric cancer cells and induces apoptosis.

STX-0119 is a selective, orally active STAT3 dimerization inhibitor. STX-0119 inhibits STAT3 transcription with an IC50 of 74 μM.

GYY4137 is a novel, water-soluble hydrogen sulfide (H2S)–releasing molecule with vasodilator and antihypertensive activity. GYY4137 shows potent anti-hepatocellular carcinoma activity through blocking the STAT3 pathway. GYY4137 also shows anti-inflammatory activity.

inS3-54A18 is a potent inhibitor of STAT3 with anti-cancer properties.

Nimucitinib is a Janus kinase (JAK) inhibitor.

Pumecitinib is a Janus kinase (JAK) inhibitor with anti-inflammatory activity.

ABBV-712 is a potent, selective inhibitor of tyrosine kinase 2 (TYK2) with EC50 of 0.01 uM, binds and stabilizes the pseudokinase (JH2) domain of TYK2.

ABT-317 (ABT317) is a potent, selective JAK1 inhibitor, inhibits IL-6-stimulated pSTAT3 (TF-1 cells, IC50=16 nM) and IL-2-stimulated pSTAT5 (T-blasts, IC50=30 nM).

ATI-1777 is a potent, selective and ATP-competitive JAK1/3 inhibitor with IC50 of 1.5/3.6/7.1/19.0 nM for JAK1/JAK2/JAK3/TYK2, respectively.

AZD0449 (AZD-0449) is a potent and highly selective JAK1 inhibitor with IC50 of 2.4 nM, displays >50-fold selectivity over TYK2 and JAK2, and no inhibition against JAK3.

CPL409116 (CPL 409116) is a potent, competitive, dual JAK and ROCK inhibitor with IC50 of 0.95/5.36//0.87/110.6/106.7 nM for JAK1/JAK2/JAK3/ROCK1/ROCK2, respectively.

MMT3-72 is a gastrointestinal locally-activating Janus kinase (JAK) inhibitor, readily converted to MMT3-72-M2 in the colon contents (JAK1 IC50=10.8 nM, JAK2 IC50=26.3 nM and TYK2 IC50=91.6 nM).

QL-1200186 is a potent, highly selective allosteric inhibitor of tyrosine kinase 2 (TYK2) with IC50 of 0.06 nM, targets pseudokinase regulatory domain (Janus homology 2, JH2) of the TYK2 protein.

A potent, selective, orally active JAK1/JAK2 inhibitor with IC50 of 3.3/2.8 nM, respectively.

YLIU-4-105-1 is a novel type II JAK2 inhibitor, binds to JAK2 kinase domain (JH1), show potential for overcoming acquired resistance to ruxolitinib.

Z583 is a potent, highly selective JAK3 inhibitor with IC50 of 0.1 nM, 4500-fold selectivity over other JAK subtypes.

DR-1-55 (DR-155) is a selective STAT3 inhibitor that covalently modifies a cysteine in the SH2 domain of STAT3.

K1836 is a small molecule Stattic analog inhibitor of STAT3 signalling.

LLL12B is a selective STAT3 inhibitor that suppresses Th17 development, specifically inhibits STAT3 and suppresses Th17 differentiation and expansion.

MC0704 (MC-0704) is a novel synthetic STAT3 pathway inhibitor, exhibits potential antitumor activity in vitro and in vivo models in docetaxel-resistant TNBC cells.

MNS1-Leu is a novel pyrazole-based small molecular inhibitor of STAT3 pathway, potently inhibit IL-6-induced STAT3 phosphorylation at 10 μM in dBT114 cells.

MNS1-MV is a novel pyrazole-based small molecular inhibitor of STAT3 pathway, potently inhibit IL-6-induced STAT3 phosphorylation at 10 μM in dBT114 cells.

ODZ10117 is a small molecule inhibitor of STAT3, effectively inhibits the level of tyrosine phosphorylated STAT3 in various cancer cell lines.

SF-1-088 is a small molecule STAT5-SH2 domain inhibitor with Ki of 8.3 uM (Stat5b), shows no affinity for Stat1 and Stat3 (Ki>25 uM).

TR120 (TR-120) is a potent small molecule STAT5 inhibitor, exhibits antiproliferative in K562 cells with IC50 of 0.12 uM, decreases STAT5 expression in imatinib-sensitive and imatinib-resistant BCR-ABL-expressing leukemia cells.

W1046 is a potent and selective STAT3 inhibitor, decreases the expression of VISTA at mRNA and protein level and inhibits proliferation and survival in AML cells.

W1131 is a potent and selective STAT3 inhibitor with Kd of 7.55 uM in surface plasmon resonance (SPR) assays, inhibits STAT3 Tyr705 phosphorylation, triggers ferroptosis and possesses potent anti-tumor effects both in vitro and in vivo.

W2014-S is a small molecule STAT3 inhibitor with binding Kd of 3.64 uM, disrupts STAT3 dimerization and selectively inhibits STAT3 signaling.

WB436B is a potent and highly selective small molecule inhibitor of STAT3, specifically targets the STAT3-SH2 domain with KD value of 94.3 nM.

WB737 is a potent and selective STAT3 inhibitor, directly binds to the STAT3 Src homology 2 (SH2) domain with KD value of 1.34 nM.

WZ-2-033 is a potent, selective STAT3 inhibitor, binds to the SH2 domain of the STAT3 protein with KD of 7.4 uM, disrupts STAT3 dimerization and significantly inhibits STAT3 signaling.