Terevalefim (ANG-3777), an hepatocyte growth factor (HGF) mimetic, selectively activates the c-Met receptor[1][2].
Axl-IN-7 (Chemie 22) is a potent AXL inhibitor. Axl-IN-7 can be used for Axl-related diseases research, for example cancers (such as acute myeloid leukemia, melanoma, breast cancer, pancreatic cancer, and glial tumors), renal disease, immune system disorders, and cardiovascular disease[1].
MCB-613 is a potent, pan steroid receptor coactivator (SRC) stimulator.Target: SRCin vitro: MCB-613 exerts the greatest activation of SRC-1 in the primary screen, is confirmed to be a strong activator of all three SRCs. MCB-613 can super-stimulate SRCs' transcriptional activity. MCB-613 increases SRCs' interactions with other coactivators and markedly induces ER stress coupled to the generation of reactive oxygen species (ROS). MCB-613 selectively and reversibly binds to the RID of SRC-3, and selectively kills cancer cells including MCF-7 (breast), PC-3 (prostate), H1299 (lung), and HepG2 (liver) cells, without toxicity to mouse primary hepatocytes and mouse embryonic fibroblasts (MEFs). MCB-613 also increases SRCs' interactions with other coactivators and markedly induces ER stress coupled to the generation of reactive oxygen species (ROS). [1]in vivo: In an MCF-7 breast cancer mouse xenograft model, MCB-613 (20 mg/kg, i.p.) significantly and dramatically inhibits the growth of the tumor while causing no obvious animal toxicity and body weight less. [1]
Gancotamab (MM-302) is a HER2-targeted antibody-liposomal Doxorubicin conjugate with antitumor activity. Gancotamab encapsulates Doxorubicin to facilitate its delivery to HER2-overexpressing tumor cells[1].
FGFR3-IN-1 (compound 1) is a fibroblast growth factor receptor (FGFR) inhibitor, with IC50s of 40 nM, 5.1 nM, and 12 nM for FGFR1, 2, and 3, respectively. FGFR3-IN-1 can be used for the research of bladder cancer[1].
Synaptamide is a potent mediator for neurogenic differentiation of NSCs acting through PKA/CREB activation.Target: in vitro: Synaptamide inhibits forskolin-mediated cAMP production (IC50 =6 μM) in CHO-HCR cells. Synaptamide decreases the viability of the LNCaP and PC3 prostate cancer cell lines (IC50=120-130 μM) grown in media containing 10% fetal bovine serum. [1] Synaptamide is an endogenous DHA metabolite with endocannabinoid-like structure, promotes neurite growth, synaptogenesis and synaptic function. Synaptamide potently induces neuronal differentiation of NSCs. Treatment of NSCs with Synaptamide at low nanomolar concentrations significantly increased the number of MAP2 and Tuj-1 positive neurons with concomitant induction of PKA/CREB phosphorylation. [2]
VEGFR-2-IN-28 (compound 12c) is a potent VEGFR-2 inhibitor with IC50 value of 0.83 µM. VEGFR-2-IN-28 induces apoptosis and has anticancer activity[1].
c-Fms-IN-7 is a cFMS inhibitor extracted from patent WO2011079076A1, example159, has an IC50 of 18.5 nM[1].
IRAK4-IN-17 (Compound 5) is a potent IRAK4 inhibitor with the IC50 of 1.3 nM[1]. IRAK4-IN-17 can be used in large B-cell lymphoma (DLBCL) research[1].
SNIPER(ABL)-024, conjugating GNF5 (ABL inhibitor) to LCL161 derivative (IAP ligand) with a linker, induces the reduction of BCR-ABL protein with a DC50 of 5μM[1].
TAS05567 (TAS-5567) is a novel potent, selective, orally available Spleen tyrosine kinase (Syk) inhibitor with IC50 of 0.37 nM; shows >70% inhibition of Syk and 4 other kinases in a panel of 192 kinases, more selective and potent than R406; suppresses induction of BLNK phosphorylation by anti-IgM in Ramos cells (IC50=1.8 nM); inhibits BCR-dependent signal transduction in Ramos cells, FcγR-mediated TNF-α production in THP-1 cells, and FcεR-mediated histamine release from RBL-2H3 cells; suppresses hind-paw swelling in a dose-dependent manner, markedly reduces histopathologic scores in rheumatoid arthritis models.
Cerdulatinib (PRT062070) is a dual JAK and SYK inhibitor with IC50s of 12, 6, 8 and 32 for JAK1, 2, 3 and SYK, respectively.
GW 441756 is a specific Tropomyosin-related kinase A (TrkA) inhibitor with an IC50 value of 2 nM; little activity to c-Raf1 and CDK2.IC50 Value: 2 nM [1]Target: TrkAin vitro: GW441756 specifically blocked TrkA-induced cell death in a dose-dependent manner, but there was no effect in uninduced cells. TrkA ability to induce γH2AX production was significantly downregulated by both K-252a and GW441756 in the absence of DNA damage inducer. In addition, it was also suppressed by K-252a during DNA damage by doxorubicin treatment, but not by GW441756 [2].
Ilorasertib hydrochloride (ABT-348 hydrochloride) is a potent and ATP-competitive multitargeted kinase inhibitor, which inhibits Aurora C, Aurora B, and Aurora A with IC50s of 1 nM, 7 nM, 120 nM, respectively. Ilorasertib hydrochloride (ABT-348 hydrochloride) also suppresses RET tyrosine kinase, PDGFRβ and Flt1 with IC50s of 7 nM, 3 nM and 32 nM, respectively[1].
ALK/ROS1-IN-1 (compound 2e) is a potent and selective anti crizotinib-resistant ALK/ROS1 dual inhibitor, with IC50s of 0.174 μM and 0.530 μM for ALK and ROS1 enzyme, respectively.
c-Fms-IN-14 (Example 76) is a c-Fms inhibitor with an IC50 value of 4 nM. c-Fms-IN-14 can be used for research of cancer and autoimmune diseases[1].
AG-1478 is a selective EGFR tyrosine kinase inhibitor with IC50 of 3 nM.
BTK-IN-22 is a BTK inhibitor (IC50: 0.9 nM). BTK-IN-22 also inhibits BLX and BMX with IC50s of 1.4 and 1.2 nM respectively. BTK-IN-22 shows improved kinase selectivity compared to Ibrutinib (HY-10997)[1]
CSF1R-IN-9 (Compound 46) is a CSF-1R inhibitor with an IC50 of 0.028 μM[1].
PTC299 is a dihydroorotate dehydrogenase (DHODH) inhibitor, has broad and potent activity against hematological cancer cells[1]. PTC299, also an orally bioavailable VEGF inhibitor, acts through posttranscriptional regulation of VEGF mRNA under conditions of cellular stress[2].
Flumatinib mesylate (HH-GV-678 mesylate), a derivative of imatinib, is a multi-kinase inhibitor with IC50 Values of 1.2 nM, 307.6 nM and 2662 nM for c-Abl, PDGFRβ and c-Kit respectively.IC50 Value: 1.2 nM (c-Abl); 307.6 nM(PDGFRβ); 2662 nM (c-Kit) [1]Target: c-Abl; c-Kit; PDGRFβin vitro: HH-GV-678 can predominantly inhibit the autophosphorylation of Bcr-Abl in K562 cell. In higher concentration, HH-GV-678 can inhibit the phosphorylation of c-Kit in Mo7e cell and the phosphorylation of PDGFR in Swiss3T3 cell, however, HH-GV-678 has no or little effect on other tyrosine kinase including EGFR/KDR/c-Src andHER2 [1]. Flumatinib effectively overcame the drug resistance of certain KIT mutants with activation loop mutations (i.e., D820G, N822K, Y823D, and A829P) [2].in vivo: The purpose of this study was to identify the metabolites of flumatinib in CML patients, with the aim of determining the main metabolic pathways offlumatinib in humans after oral administration. Ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry revealed 34 metabolites; 7 primary metabolites were confirmed by comparison with synthetic reference standards. The results show that the parent drugflumatinib was the main form recovered in human plasma, urine, and feces. The main metabolites of flumatinib in humans were the products of N-demethylation, N-oxidation, hydroxylation, and amide hydrolysis [3].
AZD4547 is a potent inhibitor of the FGFR family with IC50s of 0.2 nM, 2.5 nM, 1.8 nM, and 165 nM for FGFR1, FGFR2, FGFR3, and FGFR4, respectively.
Tomuzotuximab (Anti-Human EGFR Recombinant Antibody) is a fully human glycoengineered IgG1 monoclonal antibody against EGFR. Tomuzotuximab has anticancer effects[1].
AChE/BChE/BACE-1-IN-1 (Compound 4k) is an orally active inhibitor of AChE, BChE, and BACE-1 with IC50 values of 0.058, 0.082 and 0.115 μM against hAChE, hBChE and hBACE-1, respectively. AChE/BChE/BACE-1-IN-1 shows considerable PAS-AChE binding capability, excellent brain permeation, potential disassembly of Aβ aggregates, and neuroprotective activity against Aβ-induced stress. AChE/BChE/BACE-1-IN-1 has remarkable antioxidant potential[1].
Ack1 inhibitor 1 is a potent, selective, and orally active inhibitor of ACK1 kinase with an IC50 value of 2.1 nM. Ack1 inhibitor 1 inhibits the phosphorylation of ACK1 and activation of downstream AKT. Ack1 inhibitor 1 has anti-tumor activity[1].
APG-2449 is an orally active ALK/ROS1/FAK inhibitor. APG-2449 shows antitumor activity in mouse models of non-small cell lung cancer (NSCLC)[1].
MAX-40279 hemifumarate is a dual and potent inhibitor of FLT3 kinase and FGFR kinase. MAX-40279 hemifumarate has the potential for the research of acute myelogenous leukemia (AML) (extracted from patent WO2021180032)[1].
7-Hydroxyneolamellarin A is a natural product that could be derived from sponge Dendrilla nigra. 7-Hydroxyneolamellarin A is a potent hypoxia-inducible factor-1α (HIF-1α) inhibitor. 7-Hydroxyneolamellarin A attenuates the accumulation of hypoxia-inducible factor-1α (HIF-1α) protein and inhibits vascular epidermal growth factor (VEGF) transcriptional activity. 7-Hydroxyneolamellarin A can be used in research of cancer[1].
Tyrosine kinase-IN-7 (compound 13h) is an inhibitor of the tyrosine kinase EGFR. The IC50s for inhibiting EGFR(WT) and EGFR(T790M) are 0.630 μM and 0.956 μM respectively. Tyrosine kinase-IN-7 has antitumor activity against four cancer cell lines (HepG2, HCT-116, MCF-7, and A431) with IC50s of 13.02 μM, 10.14 μM, 12.68 μM, and 47.05 μM, respectively[1].
NVP-TAE 226 is a dual tyrosine kinase inhibitor of FAK (IC50=5.5 nM) and IGF-IR (mean IC50=0.14 μM).