| DC70528 |
JS24 |
JS24 is a potent, selective, covalent TEC family of non-receptor tyrosine kinases (BTK, ITK, TXK and BMX) inhibitor with IC50 of 7.5 and 11.1 nM for BMX and BTK, respectively.JS24 displays a strong binding affinity against all the members of TEC family, covalently inhibits BMX at Cys496.JS24 inhibits androgen-receptor positive prostate-cancer cells with GI50 of 1.5 uM.JS24 shows synergistic anti-proliferative activity in LNCaP cells in combination with AKT1/2 (AKT inhibitor), Flutamide (androgen receptor antagonist) and LY293002 (PI3K inhibitor). |
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| DC70529 |
JS25 |
JS25 is a potent, selective, covalent TEC family of non-receptor tyrosine kinases (BTK, ITK, TXK and BMX) inhibitor with IC50 of 3.5 and 5.8 nM for BMX and BTK, respectively.JS25 displays a strong binding affinity against all the members of TEC family, covalently inhibits BMX at Cys496. JS25 demonstrates intracellular target engagement in HEK293 cells (IC50=44.8 nM), 10 times greater than BMX-IN-1.JS25 inhibits androgen-receptor positive prostate-cancer cells with GI50 of 6.6 uM.JS25 shows synergistic anti-proliferative activity in LNCaP cells in combination with AKT1/2 (AKT inhibitor), Flutamide (androgen receptor antagonist) and LY293002 (PI3K inhibitor). |
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| DC70532 |
JWD-065 |
JWD-065 is a potent small molecule HIPK2 kinase inhibitor, blocks HIPK2 phosphorylation on S359/T360 and JNK activation in HEK293 cells and attenuates ER stress-induced cell death with EC50 of 641 nM. |
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| DC70541 |
KIN-8194 |
KIN-8194 (KIN8194) is a highly potent dual HCK and BTK inhibitor with IC50 of <0.495 and 0.915 nM, respectively.KIN-8194 demonstrated greater selectivity compared with A419259 with no KIT, RET, PDGFRA, EPHB6, or CDPK1 inhibition.KIN-8194 binds to gatekeeper residue Thr333 of HCK, but not to Cys481 of BTK.KIN-8194 shows robust inhibition of both HCK and BTK activity in MYD88-mutated cells, showed robust inhibition of HCK Tyr410 phosphorylation; inhibits the growth and survival of MYD88-mutated WM and ABC DLBCL cells.KIN-8194 overcomes ibrutinib resistance relatedto BTK Cys481Ser-expressing MYD88-mutated B-cell lymphoma cells, synergizes with the BCL-2 inhibitor venetoclax.KIN-8194 shows superior activity over ibrutinib in MYD88-mutated TMD-8 ABC DLBCL xenograft mouse model.KIN-8194 is active against ibrutinib resistance in BTK Cys481Ser -expressing ABC DLBCL xenograft mouse model. |
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| DC70547 |
KRCT-6j |
KRCT-6j is a potent and selective TYRO3 inhibitor, 300-fold selectivity for TYRO3 over both AXL and MerTK.KRCT-6j selectively inhibited the proliferation of TYRO3-overexpressing Ba/F3 cells, also suppressed csEV-stimulated cell migration of LNCaP-SL cells in a concentration-dependent manner.KRCT-6j diminished csEV-induced membrane localization of F-actin, reversed the increased expression and nuclear localization of YAP stimulated by csEVs.KRCT-6j significantly inhibited tumor growth in xenografts implanted with GR-H1993 cells when combined with gefitinib. |
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| DC70561 |
LDN-192960 hydrochloride |
LDN192960 (LDN 192960) is a highly potent and selective DYRK2 inhibitor with IC50 of 13 nM toward DYRK2 at 50 uM ATP.LDN192960 suppresses Thr25 RPT3 phosphorylation in a dose-dependent manner in HEK293T cells transiently overexpressing DYRK2-FLAG, with maximal effects at 1-10 uM.LDN192960 does not inhibit any of the 130+ kinases including other CMGC kinase family members that are closely related to the DYRKs.LDN192960 binds to the ATP-binding pocket of DYRK2, also potently inhibits DYRK1A, DYRK3 and Pim with IC50 of <3, 122 and 10 nM, respectively.LDN192960 perturbs proteasome activity, induces cell death, and impedes proliferation and invasion on MDA-MB-468 cells.LDN192960 impedes MM progression and delays myeloma-mediated bone degeneration.LDN192960 induces cytotoxicity in bortezomib-resistant MM, both in cells and in vivo. significantly alleviates tumor burden in standard and PDX TNBC models. |
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| DC70571 |
LS‐106 |
LS-106 is a novel, fourth‐generation EGFR inhibitor against C797S mutation, targeting both EGFR19del/T790M/C797S and EGFRL858/T790M/C797S with selectivity over EGFRwt.LS-106 potently and dose‐dependently inhibited the kinase activity of EGFR19del/T790M/C797S, EGFRL858R/T790M/C797S, EGFRL858R/T790M, and EGFR19del/T790M with IC50 values of 2.4 nM, 3.1 nM, 7.3 nM, and 74.1 nM, respectively.LS-106 exhibited much weaker effect against EGFRwt (IC50=151.5 nM) and EGFR19del (IC50=402.9 nM).LS‐106 not only strongly inhibited the EGFR‐C797S-mutant kinase but also inhibited some other kinases, such as RET, ACK1, and PDGFR‐β.LS‐106 not only inhibited the proliferation of BaF3‐EGFR19del/T790M cells (IC50= 0.09 uM) but also showed over 30‐fold stronger antigrowth activity than osimertinib in BaF3‐EGFR19del/T790M/C797S (IC50= 0.09 uM) and BaF3‐EGFRL858R/T790M/C797S (IC50= 0.12 uM) cells, respectively, elicits significant cell apoptosis in EGFR–triple‐mutant cells.Oral administration of LS‐106 (30 and 60 mg/kg) potently inhibited tumor progression in PC‐9‐OR NSCLC xenograft model with TGI of 83.5% and 136.6%, respecitvely. |
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| DC70582 |
M4K2234 |
M4K2234 is a potent, selective ALK1 (ACVRL1) and ALK2 (ACVR1) protein kinase inhibitor with IC50 of 7 and 14 nM, respectively.M4K2234 inhibits only ALK1/2 and one additional off target (TNIK) by kinome-wide screening against 375 protein kinases at 1 uM.M4K2234 demonstrated in cell based target engagement assays with an IC50 of 83nM for ALK1 and 13 nM for ALK2.M4K2234 exhibits only very weak potency against ALK4/5.M4K2234 affects phosphorylation of SMAD1/5/8 that corresponds to BMP branch of signalling which is mediated, besides others, also by ALK1/2 kinases.M4K2234 has only a very weak effect on SMAD2/3 phosphorylation that corresponds to TGF beta branch of signalling which is mediated mostly via ALK4/5/7. |
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| DC70628 |
MU1700 |
MU1700 is a potent, selective ALK1 (ACVRL1) and ALK2 (ACVR1) protein kinase inhibitor with IC50 of 13 and 6 nM, respectively.MU1700 inhibits only ALK1/2/6 and no additional off targets by kinome-wide screening against 369 protein kinases at 1 uM.MU1700 affects phosphorylation of SMAD1/5/8 that corresponds to BMP branch of signalling wchich is mediated also by ALK1/2 kinases.MU1700 is suitable chemical probe for in vivo disease models, and has remarkably high brain penetrance (mice, PO, 1 g/kg). |
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| DC70629 |
MU1787 |
MU1787 is a potent, highly selective HIPK inhibitor with IC50 of 285/123/283 nM for HIPK1/2/3, repectively.MU1787 is highly selective across the kinome in a broad panel of 373 human kinases, does not inhibits HIPK4 at 10 uM. |
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| DC70666 |
NSC81111 |
NSC81111 is a highly potent EGFR-TK inhibitor with IC50 of 0.15 nM;
NSC81111 displays stronger antiproliferative activities than erlotinib with IC50 values of <10 uM overexpressed EGFR-TK cancer cell lines: A431 and HeLa. |
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| DC70670 |
ONO-7579 |
ONO-7579 (ONO7579) is a novel potent, selective, orally available pan-TRK inhibitor.BDNF significantly increased TRKB phosphorylation in GBC cells and the effects were abrogated by ONO-7579, suppress proliferation in a dose-dependent manner in TYGBK-1 cells.ONO-7579 inhibited BDNF/TRKB-induced migration and invasiveness, particularly in GBC cells harboring wild-type KRAS.ONO-7579 reduced invasiveness of gallbladder cancer (GBC) cells through inhibiting epithelial–mesenchymal transition (EMT) via the extracellular signal-regulated kinase (ERK) or protein kinase B (AKT) pathway. |
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| DC70689 |
PF-07265807 |
PF-07265807 (PF 07265807) is a potent, selective dual Axl/Mer inhibitor, blocks Axl- and Mer-mediated signal transduction pathways, and inhibits proliferation and migration of Axl- and Mer-overexpressing tumor cells. |
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| DC70734 |
RET agonist BT44
Featured
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RET agonist BT44 is a novel, specific RET agonist, promotes RET phosphorylation and selectively activates downstream cascades in the cells expressing GFL receptors.BT44 has no effect on TrkA and TrkB receptors; In GFRα1/RET expressing cells, 10–50 µM of BT44 increased the activity of luciferase reporter by approximately two fold (P<0.0001).BT44 dose-dependently stimulated neurite outgrowth from DRG sensory neurons and its efficacy was comparable to that of ARTN.BT44 alleviated mechanical hypersensitivity in surgery- and diabetes-induced rat models of neuropathic pain. |
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| DC70764 |
sCSF1Rinh |
sCSF1Rinh is a CNS-penetrant, potent and selective small-molecule CSF1R inhibitor, binds to CSF1R in a DFG-out conformation.is highly selective for CSF1R as compared to other kinases with a selectivity score of S(35)=0.005, sCSF1Rinh exhibited excellent pharmacokinetic properties including good oral bioavailability and CNS penetrance.sCSF1Rinh (500 nM) blocks these phosphorylation events in CSF1 (100 ng/mL) stimulation of BV2 microglia.sCSF1Rinh inhibited murine bone marrow-derived macrophage proliferation with IC50 of 22 nM, sCSF1Rinh significantly depletes microglia in a concentration-dependent manner in murine mixed glial cultures (IC50=188 nM).sCSF1Rinh reduced the number of microglia and infiltrating macrophages in an acute LPS model, with diminished microglial/macrophage proliferation and attenuated inflammatory response.sCSF1Rinh also suppressed a deleterious microglial response in the C57BL/6 EAE (experimental autoimmune encephalomy) model as well as the MOG peptide-induced non-obese diabetic EAE model of progressive MS (NOD-EAE) and improved neurological impairments in both models. |
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| DC70792 |
SPH5030 |
SPH5030 is a selective, potent, and irreversible HER2 mutants inhibitor with IC50 of <1 nM against HER2 D769H, D769Y, V777L and R896C mutants.SPH5030 exhibits high relative HER2 selectivity compared with neratinib and pyrotinib.SPH5030 shows significant in vivo antitumor efficacy in xenograft mouse models, especially in a HER2 mutation A775_G776insYVMA xenograft mouse mode. |
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| DC70795 |
SR-302 |
SR-302 (SR302) is a potent, selective cell-active dual DDR/p38 inhibitor with IC50 of 23/18/125/196 nM for DDR1/DDR2/p38α/p38β, respectively. |
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| DC70820 |
SYHA1815 |
SYHA1815 (SYHA-1815) is a novel potent, selective RET inhibitor, inhibits the kinase activity of RET wild type (IC50=0.9 nM) and V804 mutant (IC50=3.1 nM).SYHA1815 demonstrated approximately 20-fold selectivity for RET over KDR, exhibited a favorable selectivity profile, with> 100-fold selectivity over 347 kinases, and >10-fold selectivity over 44 other kinases in a panel of 395 kinases.SYHA1815 significantly inhibited RET phosphorylation and activation of its key adaptor protein SHC and the downstream signaling molecules p-AKT and p-ERK1/2 in classical RET mutant-driven MTC cell line TT (RETC634W), effectively inhibited p-RET, p-SHC, and downstream p-AKT and p-ERK activity.SYHA1815 inhibited RET-induced cell proliferation and overcame V804 mutants (TT cell proliferation IC50<1.6 nM), suppressed RET-driven cell proliferation via cell-cycle arrest through c-Myc downregulation.SYHA1815 showed potent antitumor efficacy against RET- and RET gatekeeper mutant-driven cancers in vivo. |
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| DC70835 |
TG-1701 |
TG-1701 (Edralbrutinib, TG1701) is a irreversible, orally available, potent and highly specific BTK inhibitor with Kd of 3 nM, IC50 of 6.7 nM, more selective than ibrutinib.TG-1701 exerts similar activity than the first-in-class BTKi ibrutinib, although with greater selectivity, in in vitro and in vivo models of B-NHL.TG-1701 impaired BCR downstream signaling in a concentration-dependent manner in IgM-stimulated cells, with maximal effects observed at 100 nM for TG-1701.TG-1701 shows mean GI50 of 6.4 uM in a set of 10 parental B-NHL cell lines (MCL cell lines GI50=4.3 uM).TG-1701 blunts Ikaros gene signature, including YES1 and MYC, in early-responder patients as well as in BTKi-sensitive B-NHL cell lines and xenografts. |
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| DC70843 |
THRX-144644 |
THRX-144644 (THRX144644) is a potent, lung-selective ALK5 inhibitor with IC50 of 0.14 nM, inhibits p-SMAD3 in a BEAS2B cell line with IC50 of 23 nM;
THRX-144644 displays high selectivity in a broad secondary pharmacology panel with exception of e Lymphocyte CellSpecific Protein-Tyrosine Kinase (LCK, IC50=140 nM).
THRX-144644 demonstrated favorable TGFβ pathway pharmacodynamic inhibition in lung while minimizing key systemic toxicities. |
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| DC70869 |
UNC5293 |
UNC5293 (UNC-5293) is a potent, highly selective, orally available inhibitor of MER receptor tyrosine kinase (MERTK) with IC50 0.9 nM, Ki 0.19 nM.UNC5293 exhibits an excellent Ambit selectivity score (S50 (100 nM) = 0.041), and displays 50-100 fold selectivity over other two TAM Receptor member kinases (Tyro3 and Axl).UNC5293 demonstrated potent and selective inhibition of MERTK in cell-based assays. has excellent mouse PK properties (7.8 h half-life and 58% oral bioavailability) and was active in bone marrow leukemia cells in a murine model. |
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| DC70879 |
Utatrectinib |
Utatrectinib (AZD7451, AZ12607092) is a potent, selective, small molecule pan-Trk (NTRK) inhibitor with IC50 of 0.2-3.0 nM against TrkA, TrkB, and TrkC.Binding of AZD7451 to TrkA, TrkB, and TrkC would be expected to inhibit responses associated with NGF, BDNF, and NT3, respectively.AZD7451 completely blocked TrkC activation and associated tumorigenic behaviors at sub-micromolar concentrations in normal salivary gland tissue.AZD7451 showed efficacy and low toxicity in pre-clinical studies on adenoid cystic carcinoma (ACC) tumors engrafted in mice.AZD7451 potently inhibited in vitro growth and proliferation of the KM12 cell line harboring the NTRK1-fusion at 2 nM, AZD7451 inhibited proliferation of H460 cells at 5 nM, with TRKA phosphorylation inhibition. |
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| DC70909 |
XMU-MP-3 |
XMU-MP-3 is a potent, selective, noncovalent BTK inhibitor with IC50 of 10.7 nM and 17.0 nM for BTK WT and BTK C481S mutation.XMU-MP-3 inhibited BTK‐transformed Ba/F3 cell proliferation with an IC50 of 11.4 nM, with negligible anti‐proliferative effects on parental wild‐type Ba/F3 cells (IC50>10 uM).XMU‐MP‐3 inhibited both the autophosphorylation and trans‐phosphorylation of BTK at residues Y223 and Y551, in a dose‐dependent manner in BTK‐transformed Ba/F3 cells at concentrations as low as 100 nM and completely suppressed at 1,000 nM.XMU‐MP‐3 was considerably less potent (IC50, 2,815 nM) against proliferation of BTK(T474M)‐transformed Ba/F3 cells.XMU‐MP‐3 inhibits the growth of malignant B‐cells, inhibited phosphorylation of PLCγ2 at Y1217 and Y759, substantially suppresses tumour growth in mouse xenograft models.XMU‐MP‐3 maintained inhibitory potency with an IC50 of 182.3 nM against BTK(C481S)‐Ba/F3 cells and with an IC50 of 17.0 nM in biochemical assays, suppressed ibrutinib‐resistant BTKC481S mutation in vivo. |
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| DC70910 |
XMU-MP-5 |
XMU-MP-5 is a new-generation potent and selective ALK inhibitor (IC50=4.15 nM) to overcome crizotinib resistance mutations, including L1196M and G1202R;
XMU-MP-5 significantly induced apoptosis in EML4-ALK Ba/F3 cells did not affect apoptosis in wild-type Ba/F3 cells.
XMU-MP-5 shows highest binding affinities for ALK and its mutants ALK(C1156Y) and ALK(L1196M), with K d values of 0.57, 0.4, and 0.77 nM, respectively.
XMU-MP-5 blocks ALK signaling pathways and inhibits the proliferation of cells harboring either wild-type or mutant EML4-ALK in vitro and suppresses tumor growth in xenograft mouse models in vivo.
XMU-MP-5 induces significant regression of lung tumors in two genetically engineered mouse (GEM) models. |
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| DC71030 |
Demethylasterriquinone B1 |
Demethylasterriquinone B1 is a selective insulin receptor activator. Demethylasterriquinone B1 stimulates tyrosine phosphorylation of the IR β subunit, and the activation of PIK3 and AKT. |
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| DC71064 |
JH-XIV-68-3 |
JH-XIV-68-3 is a selective macrocyclic inhibitor of DYRK1A/B. JH-XIV-68-3 displays selectivity for DYRK1A and close family member DYRK1B in biochemical and cellular assays. JH-XIV-68-3 demonstrates antitumor efficacy in head and neck squamous cell carcinoma (HNSCC) cell lines. |
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| DC71094 |
NT219 |
NT219 is a potent and dual inhibitor of insulin receptor substrates 1/2 (IRS1/2) and STAT3. IRS1/2 and STAT3 are major signaling junctions regulated by various oncogenes. NT219 affects IRS1/2 degradation and inhibits STAT3 phosphorylation. NT219 has the potential for the research of cancer diseases. |
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| DC71100 |
PD 174265 |
PD 174265 is a potent, cell-permeable, reversible, and selective inhibitor of EGFR with an IC50 of 450 pM. |
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| DC71141 |
D5261 |
D5261 is a potent, type III allosteric tropomyosin-related kinase A (TrkA) inhibitor. |
|
| DC71143 |
SNIPER(TACC3)-11 |
SNIPER(TACC3)-11 is a potent FGFR3-TACC3 degrader. SNIPER(TACC3)-11 reduces FGFR3-TACC3 protein levels and suppressed the growth of FGFR3-TACC3 positive cancer cells. |
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