COB-187 (COB187) is a highly potent and selective inhibitor of GSK-3 with IC50 of 22/11 nM against GSK-3α/GSK-3β.COB-187 inhibits GSK-3 phosphorylation of β-catenin and, albeit to a lesser extent, glycogen synthase.COB-187 increases the protein level of β-catenin in RAW 264.7 macrophages.COB-187 enhances β-catenin localization to the perinuclear and nuclear region in THP-1 macrophage, does not change the β-catenin mRNA level.COB-187 significantly increases the expression of the Wnt target gene cyclin D1, reduces the phosphorylation of tau in HEK293 cells transfected with tau expression vector.COB-187 inhibits only 3 kinases at >40% in a panel of 414 kinase assays, more selective relative to Tideglusib.

CNBDA is a novel selective Src homology phosphotyrosine phosphatase 2 (SHP2) inhibitor with IC50 of 5 uM, 25-fold selectivity over SHP1.Treatment HER2-positive BC cells with CNBDA suppressed cell proliferation in 2D culture, anchorage-independent growth in soft agar, and mammosphere (tumorisphere) formation in suspension cultures in a concentration-dependent manner.CNBDA inhibited EGF-induced signaling and expression of HER2 by inhibiting the PTPase activity of SHP2 in BC cells.

Cl-OCH3 is an antagonist of nuclear receptor NR4A1, decreases PD-L1 protein expression in MDA-MB-231 and 4T1 cells with EC50 of 4.4 and 4.1 uM, respectively; Cl-OCH3 decreased expression of PD-L1 mRNA, promoter-dependent luciferase activity, and protein. In in vivo studies using a syngeneic mouse model bearing orthotopically injected 4T1 cells, Cl-OCH3 decreased tumor growth and weight and inhibited lung metastasis. Cl-OCH3 also decreased expression of CD3+/CD4+/CD25+/FoxP3+ regulatory T cells and increased the Teff/Treg ratio.

CLK4 inhibitor 96 is a novel potent CLK4 inhibitor with IC50 of 57.5 nM.

CK2 inhibitor KN2 is a potent, highly selective, cell-permeable, bivalent CK2 inhibitor, binds to CK2α- and CK2α′-based CK2 holoenzymes with Ki of 6.1 nM (CK2α2β2) and 4.0 nM (CK2α′2β2).KN2 inhibits CK2α- and CK2α′-based CK2 holoenzymes with IC50 of 19.3 nM (CK2α2β2) and 15.6 nM (CK2α′2β2) at 100 uM ATP.KN2 downregulated the CK2-dependent phosphorylation level of Akt phosphorylation at Ser129 (p-Akt S129).

CJ-1639 (CJ1639) is a potent, highly selective dopamine D3 receptor (D3R) full agonist with Ki of 0.5 nM, >5,000-fold selectivity over D1 and D2 receptors in binding assays.CJ-1639 binds to human D3 receptor with a K(i) value of 3.61 nM and displays over >1000-fold selectivity over human D1 and D2 receptors.CJ-1639 is an excellent pharmacological tool to elucidate the role of the D3 receptor in different neurological conditions in animal models.

CIGB-300 (P15-Tat) is a cell-permeable cyclic peptide that modulates CK2 (CSNK2) activity by binding to the phosphoacceptor site on CK2 targets, abrogates the CK2 phosphorylation by blocking recombinant substrates in vitro.CIGB-300 (P15-Tat) induced apoptosis as evidenced by rapid caspase activation and cellular cytotoxicity in a variety of tumor cell lines (HSCLC H-82 cell IC50=20 uM).CIGB-300 (P15-Tat) demonstrated substantial regression of the tumor mass C57BL6 mice bearing day 7-established solid tumors.CIGB-300 (P15-Tat) reduced breast cancer cell growth in MDA-MB-231, MCF-7 and F3II cells, exerting a pro-apoptotic action and cell cycle arrest. CIGB-300 decreased cell adhesion, migration and clonogenic capacity of malignant cells.CIGB-300 may interfere with the SARS-CoV-2 life cycle within infected human cells.

Ciapavir (SBI-0953294, cIAP1 antagonist for viral reactivation) is a bivalent, next-generation, Smac mimetic and antagonist of cIAP1 as latency-reversing agent (LRA), specifically and potently promote HIV-1 latency reversal activity both in vivo.Ciapavir's latency reversal activity is dependent on the NIK-dependent NF-κB signaling.Ciapavir exhibits substantially greater potency and efficacy as an LRA, inducing comparable levels of latency reversal at concentrations 10- to 1,000-fold lower than the first-generation molecule SBI-0637142, without an increase in cytotoxicity.Ciapavir does not trigger cytokine release or T cell activation.Ciapavir is capable of increasing latent HIV-1 expression in ART-treated BLT mice in vivo and may therefore prove useful in "shock and kill" approaches to HIV-1 cure.

CFT-14441 is a potent and selective BRD9 BiDAC degrader with DC50 of 39 nM (2h), high selectivity over BRD4 abd BRD7.CFT-14441 efficiently degrades endogenous BRD9 in the Yamato-SS synovial sarcoma cell line, results in growth inhibition of BAF-perturbed HSSYII synovial sarcoma cells but not BAF-wild type SW982 soft tissue sarcoma cells.CFT-14441 demonstrates efficacy in both cell-derived and patient-derived models of synovial sarcoma (IV or IP dosing).

CFI-400945 is a potent, highly selective, orally available PLK4 inhibitor with Ki of 0.26 nM and IC50 of 2.8 nM, does not significantly inhibits PLK1/2/3 at 50 uM; causes dysregulated centriole duplication, mitotic defects, and cell death in multiple cancer cell lines (A549 GI50=5 nM, OVCAR-3 GI50=18 nM); significantly inhibits human cancer xenografts; causes polyploidy, growth inhibition, and apoptotic death of murine and human lung cancer cells, despite expression of mutated KRAS or p53, produces supernumerary centrosomes and mitotic defects in lung cancer cells.

CDDD2-94 is a highly potent and selective CDK4 inhibitor with Ki of 2 nM, >140-fold selective for CDK4 over CDK6 (Ki=279 nM).CDDD2-94 is ineffective against other members of the CDK family, displays high selectivity against a panel of 369 human kinases at 1uM, with exceptionally selective-CLK, DYRKs and MYLK4 were the only kinases targeted potently.CDDD2-94 is the most selective CDK4 inhibitor identified to date.CDDD2-94 demonstrated antiproliferative activityagainst MV4-11 and MDA-MB-453 cell lines with GI50 of 0.107 and 0.325 uM respectively.CDDD2-94 inhibits S780-phosphorylated Rb (pRb(S780)) and decreases transcription of Rb1 and E2F-target genes in MDA-MB-453 cells.CDDD2-94 is well tolerated and efficacious in preclinical OC xenograft model, CDDD2-94 provides better safety profile than palbociclib towards the bone marrow.

CDD-1102 (CDD1102) is a potent, selective second bromodomain (BD2) of BRDT and BRD4 inhibitor with IC50 of 7 and 25 nM, >1,000-fold and 300-fold selectivity over BRDT-BD1 and BRD4-BD1.

CCX-6239 is a novel potent, orally available CCR4 inhibitor with potential utility in the treatment of allergic airways disease.

CCT369347 (CCT-369347) is potent selective inhibitor of BCL-6 with TR-FRET IC50 of 26 nM.CCT369347 demonstrated antiproliferative activity in a panel of BCL6-positive lymphoma cell lines (OCI-Ly1, SU-DHL-4, and SU-DHL-6) with IC50 of 1.68-3.45 uM, with weaker activity against low BCL6 expression cells and noncytotoxocity. CCT369347 inhibits BCL6 in a cellular assay with a submicromolar IC50 and shows promising early PK.

CCR2 inhibitor SD-24 is a potent selective CCR2 antagonist with pKi of 8.5.

CCR2 covalent-IN-14 is a covalent, negative allosteric modulator (NAM) of CCR2, binds to intracellularly pocket of CCR2 with Ki of 4 nM.CCR2 covalent-IN-14 is more potent than non-covalent analogue and wash-resistant in functional assays (IC50=33 nM in GTPγS binding assay on U2OS-CCR2 cell membranes, IC50=4 nM in β-arrestin recruitment assays).CCR2 covalent-IN-14 displays little to no inhibitory potency on CCR1 and CCR5.The affinity of CCR2 covalent-IN-14 for both the C70S and C75S CCR2 mutants is significantly decreased compared to WT CCR2.

CBS1194 is a novel specific fusion inhibitor for group 2 influenza viruses, inhibits IAVs bearing group 2 HAs (pseudo-H7, EC50=0.25 uM).CBS1194 displays no inhibition against both pseudo-H5 and pseudo-Lassa.CBS1194 exhibitss potency agianst group II influenza viruses influenza A/rhea/North Carolina/1993 (H7N1) and A/Hong Kong/1/1968 (H3N2) with EC59 of 3.17 and 1.60 uM, respectively.CBS1194 displays no inhibitory activity against group 1 influenza viruses, including A/Puerto Rico/8/1934 (H1N1) and A/Viet Nam/1203/04 (H5N1).CBS1194 acts at an early stage of viral infection, inhibits viral HA mediated hemolysis, and prevents the low pH-induced conformational change of HA.The substitutions K1172N and T301A but not D71N to confer resistance to CBS1194.

CBR417 (CBR-417) is a potent and selective antiwolbachial activity compound (Anti-Wolbachia wMel In vitro HCI cell-based assay IC50=21 nM, IC90=1640 nM).CBR417 demonstrates potent antiwolbachial activity was confirmed in L. sigmodontis, Brugia malayi, and Onchocerca ochengi in vivo preclinical models of filarial disease.CBR417 demonstrates in vitro selectivity against Loa loa (a safety concern in endemic areas).

CBK288679 (CBK79) is a novel compound that impairs both protein degradation by the ubiquitin-proteasome system (UPS) and autophagy.CBK79 inhibits cell viability of MelJuSo Ub-YFP cells with 72h IC50 of 0.22 uM, CBK79-inflicted cell death was caspase-independent.CBK79 causes accumulation of ubiquitin-dependent and -independent proteasome substrates.CBK79 induces non-canonical lipidation of MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3 beta) that requires ATG16L1 but is independent of the ULK1 and class III phosphatidylinositol 3-kinase (PtdIns3K) complexes.CBK79 (10 uM) induces proteotoxic stress and the heat shock response in HOS GFP-LC3B cells.CBK79 has unique features as it inhibits both ubiquitin-dependent and -independent degradation of short-lived proteins by the UPS, as well as the degradation of long-lived proteins by autophagy.

CBK006377 (CBK77) is a small molecule inhibitor of the ubiquitin-proteasome system (UPS) with EC50 of 4.3 uM in MelJuSo Ub-YFP cells (6h treatment).CBK77 (16h treatment, 10 uM) causes an irreversible, global impairment of the UPS collapse, accompanied by a general accumulation of ubiquitylated proteins and caspase-dependent cell death.CBK77 causes a global impairment of ubiquitin-dependent proteasomal degradation without global inhibition of proteasome or DUB activity.NAD(P)H:quinone oxidoreductase 1 (NQO1) is a critical factor for CBK77-mediated UPS impairment, CBK77 is an NQO1 substrate, efficiently metabolized by NQO1.CBK77 reduces growth of NQO1-proficient human cancer cells and xenograft tumors in mice without overt signs of toxicity.

CaNDY is a highly potent rectifier of the aberrant splicing, potently inhibits DYRK1A, DYRK1B, CLK1/CLK2/ with IC50 of 21.6/68.3/116 nM in in vitro kinase assays.CaNDY is a potent and selective inhibitor of DYRK family kinases, CaNDY induces selective degradation of DYRK1A, and inhibits catalytic activity of recombinant DYRK1A with IC50 value of 7.9 nM by competing with ATP, antagonizes the CDC37 interaction with DYRK1A.CaNDY demonstrated CFTR pseudo exon suppression with EC50 of 1.2 uM, 20.4 times lower than that of TG003.Splice modulation by CaNDY is mediated by its CLK-inhibition activity.CaNDY, but not CFTR modulator VX-809, rescues mature CFTR expression from the CFTR gene with the 3,849 + 10 kb C>T mutation, suppresses SRSF phosphorylation.CaNDY (3 uM) treatment rescued CFTR channel activity from CFTRC>T-GFP at an extent comparable to that of CFTRWT-GFP, demonstrating a restoration of functional CFTR expression.

CaMK1D-IN-18 is a potent, selective CaMK1D inhibitor with IC50 of 31 nM, >150-fold greater activity against CaMK1D than all non-CaMK1 kinases.CaMK1D-IN-18 improves insulin sensitivity and glucose control in the diet-induced obesity mouse model after both acute and chronic administration.

CAM833 (CAM-833) is a potent, specific chemical inhibitor of the RAD51-BRCA2 interaction and RAD51 oligomerization with Kd of 366 nM; CAM833 inhibited RAD51 foci formation 6 h after exposure to 3 Gy IR, in a concentration-dependent manner with an IC50 of 6 uM, causeed a concentration-dependent decrease in RAD51 foci accompanied by increased DNA damage in A549 cells. CAM833 inhibted RAD51 molecular clustering at DNA damage sites visualized by SMLM, suppressed homologous recombination and potentiated cell-cycle arrest. CAM833 potentiated the growth suppressive effect of PARP1 inhibition in BRCA2 wild-type cells, as well as dose-dependent growth inhibition when combined with ionizing radiation.

CAD204520 (CAD 204520) is a potent, specific, oral available inhibitor of SERCA (Sarco/Endoplasmic Reticulum Calcium ATPase) with IC50 of 0.34 uM; CAD204520 preferentially targets mutated over wild-type NOTCH1 proteins in T-All and MCL. CAD204520 preferentially inhibited the Ca2+-ATPase by reducing SERCA's ATP hydrolysis activity with an IC50=0.34 uM as compared to the Na+/K+-ATPase (IC50 8.30 uM) and the H+-ATPase. CAD204520 modulates Notch1 signaling, and preferentially inhibits NOTCH1 mutated cancers. CAD204520 suppresses NOTCH1-mutated leukemic cells in a T-ALL xenografted model without causing cardiac toxicity.

C5 complement inhibitor 7 (C5-IN-7) is a potent, small-molecule inhibitor of C5 complement protein with serum assay IC50 of <5 nM (2% human serum complement inhibition).C5-IN-7 demonstrated excellent potency and good aqueous solubility, inhibited MAC deposition with IC50 of 1 uM in a complement inhibition assay using 50% human whole blood.The C5 triple mutants (C704R, V705I and N707H) were not inhibited by C5 complement protein inhibitor 7 up to 100 uM.C5 complement protein inhibitor 7 binds within the predicted pocket between the C5a and MG8 domains in close proximity to the C5 convertase cleavage site (R751-L752).

BY27 (BD2 inhibitor BY27) is a potent, highly selective BET BD2 inhibitor with Ki of 8.9/8.2/14.2 nM for BRD2/3/4-BD2 respectively.BY27 displays 38-fold selectivity for BRD2-BD2 over BRD2-BD1.BY27 showed good antitumor activity in the MV4-11 xenograft model with an improved in vivo tolerance in mice compared with I-BET762.

BX471 is a potent, selective, orally available CCR1 antagonist with Ki of 1 nM for hCCR1, displays 100 times less affinity for rat CCR1; shows 10,000-fold selectivity for CCR1 compared with 28 GPCRs (); displays CCR1 ligands MIP-1α, RANTES, and MCP-3 with high affinity (Ki=1-5.5 nM), inhibits a number of CCR1-mediated effects including Ca(2+) mobilization, increase in extracellular acidification rate, CD11b expression; effectively reduces disease in a rat experimental allergic encephalomyelitis model of multiple sclerosis.

BVQ1814 (BVQ-1814) is a highly effective fluorescent probe targeting PDE10A with highly potent affinity (IC50=0.9 nM), >1000-fold subfamily selectivity.

Burkfloxacin (BFX) is a fluoroquinolone analog that potently inhibits growth of intracellular Burkholderia.Burkfloxacin is active against other gram-negative organisms in vitro, showing similar potency to the widely used fluoroquinolone, ciprofloxacin (Cip), against Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853.Burkfloxacin near-completely inhibits plaque formation by Bt and Bp at concentration of 0.5 uM.Burkfloxacin functions as a canonical fluoroquinolone by inhibiting the negative DNA supercoiling activity of E. coli DNA gyrase.Treatment with Burkfloxacin was significantly more effective than ceftazidime, the current antibiotic of choice, for improving survival and decreasing bacterial counts in major organs in a murine model of fulminant respiratory melioidosis.

BTX306 (BTX-306) is a novel protein homeostatic modulator, potently reduces levels of GSPT1, eRF1, CK1α, MCL-1, and c-MYC in myeloma cells, overcomes bortezomib and lenalidomide resistance.BTX306 is much more potently reduced human-derived myeloma cell line viability, with median inhibitory concentrations in the single nanomolar range versus micromolar values for lenalidomide or pomalidomide, and more potently activated caspases 3/8/9.BTX306 did not impact viability of murine hematopoietic cells in an in vivo model, demonstrating its specificity for human cereblon.BTX306 did show some reduced activity in lenalidomide-resistant cell line models but nonetheless retained its nanomolar potency in vitro, overcame bortezomib resistance, and was equipotent against otherwise isogenic cell line models with either wild-type or knockout TP53.BTX306 demonstrated strong activity against primary CD138-positive plasma cells, showed enhanced anti-proliferative activity in combination with bortezomib and dexamethasone.BTX306 was effective in an in vivo systemic model of multiple myeloma.