Mutated EGFR-IN-2 (compound 91) is a mutant-selective EGFR inhibitor extracted from patent WO2017036263A1, which potently inhibits single-mutant EGFR (T790M) and double-mutant EGFR (including L858R/T790M (IC50=＜1nM) and ex19del/T790M), and can suppress activity of single gain-of-function mutant EGFR (including L858R and ex19del) as well. Mutated EGFR-IN-2 shows anti-tumor antivity[1].
BCPyr is a new candidate BTK degrader (DC50 = 800 nM).
KB SRC 4 is a potent, and highly selective c-Src inhibitor, with a Ki of 44 nM and a Kd of 86 nM, and shows no inhibition on c-Abl up to 125 μM; KB SRC 4 has antitumor activity.
EGFR-IN-87 is a EGFR tyrosine kinase inhibitor. EGFR-IN-87 has IC50 value of 3.1 nM, 1.3 nM and 7.1 nM for EGFR_d746-750, EGFR_L858R/T790 and EGFR_WT in A431 cells, respectively. EGFR-IN-87 can be used for cancer diseases research[1].
LC-MB12 is an orally active PROTAC compound targets FGFR2 degradation with a DC50 of 11.8 nM. LC-MB12 contains BGJ398 (a FGFR2 inhibitor), PROTAC linker and CRBN.LC-MB12 inhibits FGFR2 signaling in gastric cancer cells and has anti-tumor activity[1].
Sovleplenib (HMPL-523) is a highly potent, orally available and selective SYK inhibitor with an IC50 of 25 nM. Anti-tumor activity. Sovleplenib can be used for the research of immune thrombocytopenia (ITP)[1].
Amuvatinib (MP-470) is a potent and multi-targeted inhibitor of c-Kit, PDGFRα and Flt3 with IC50 of 10 nM, 40 nM and 81 nM, respectively.IC50 Value: 10 nM(c-KitD816H); 40 nM(PDGFRαV561D); 81 nM(Flt3D835Y) [1]Target: c-Kit; PDGFRα; FLT3in vitro: The hydrochloride salt of MP-470 also inhibits several mutants of c-Kit, including c-KitD816V, c-KitD816H, c-KitV560G, and c-KitV654A, as well as a Flt3 mutant (Flt3D835Y) and two PDGFRα mutants (PDGFRαV561D and PDGFRαD842V), with IC50 of 10 nM to 8.4 μM. MP-470 potently inhibits the proliferation of OVCAR-3, A549, NCI-H647, DMS-153, and DMS-114 cells, with IC50 of 0.9 μM–7.86 μM [1]. MP-470 also inhibits c-Kit and PDGFRα, with IC50 values of 31 μM and 27 μM, respectively. MP-470 demonstrates potent cytotoxicity against MiaPaCa-2, PANC-1, and GIST882 cells, with IC50 of 1.6 μM to 3.0 μM. MP-470 also binds to and inhibits several c-Kit mutants, including c-KitK642E, c-KitD816V, and c-KitK642E/D816V [2]. In MDA-MB-231 cells, MP-470 (1 μM) inhibits tyrosine phosphorylation of AXL [3]. In LNCaP and PC-3, but not DU145 cells, MP-470 exhibits cytotoxicity with IC50 of 4 μM and 8 μM, respectively, and induces apoptosis at 10 μM. In LNCaP cells, MP-470 (10 μM) elicits G1 arrest and decreases phosphorylation of Akt and ERK1/2 [4].in vivo: In mice xenograft models of HT-29, A549, and SB-CL2 cells, MP-470 (10 mg/kg–75 mg/kg via i.p. or 50 mg/kg–200 mg/kg via p.o.) inhibits tumor growth [1]. In mice bearing LNCaP xenograft, MP-470 (20 mg/kg) combined with Erlotinib significantly induces tumor growth inhibition (TGI) [4].
Sennoside B is an anthraquinone glycoside, found in large quantities in leaves and pods of Senna (Cassia angustifolia)[1]. Sennoside B can inhibit PDGF-stimulated cell proliferation by binding to PDGF-BB and its receptor and by down-regulating the PDGFR-beta signaling pathway[2].
Insulin peglispro (BIL) is a basal insulin with a flat, prolonged activity profile. Insulin peglispro can exhibit better glycaemic control compared to conventional insulins[1].
SIAIS178 is a potent and selective BCR-ABL degrader based on PROTAC technology with an IC50 of 24 nM. SIAIS178 causes effective degradation of BCR-ABL protein by recruiting Von Hippel-Lindau (VHL) E3 ubiquitin ligase. SIAIS178 has anticancer activity[1].
AS-1763 is a potent, selective, noncovalent, and orally available inhibitor of Bruton’s tyrosine kinase (IC50 = 0.85 nM).
DMNQ is a redox cycling agent that generates both superoxide and hydrogen peroxide intracellularly in a concentration dependent manner. DMNQ increases ROS generation[1].
Tilvestamab (BGB149) is a humanized anti-AXL antibody that blocks AXL-mediated cell signaling. Tilvestamab significantly inhibits Gas6-induced AXL activation in 786-0-Luc RCC cells and inhibits downstream AKT phosphorylation. Tilvestamab can be used in cancer research, particularly in AXL overexpressing renal cell carcinomas[1].
LDN-192960 hydrochloride is an inhibitor of Haspin and Dual-specificity Tyrosine-regulated Kinase 2 (DYRK2) with IC50s of 10 nM and 48 nM, respectively[1].
Anticancer agent 56 (compound 4d) is a potent anti-cancer agent with drug-likeness properties, possessing anticancer activity against several cancer cell lines (IC50<3 μM). Anticancer agent 56 induces cell cycle arrest at G2/M phase and triggers mitochondrial apoptosis pathway. Anticancer agent 56 acts by accumulation of ROS, up regulation of BAX, down regulation of Bcl-2 and activation of caspases 3, 7, 9[1].
TAK-020 is a covalent Btk inhibitor, which becomes the clinical candidate.
MBM-55S is a potent NIMA-related kinase 2 (Nek2) inhibitor with an IC50 of 1 nM. MBM-55S shows a 20-fold or greater selectivity in most kinases with the exception of RSK1 (IC50=5.4 nM) and DYRK1a (IC50=6.5 nM). MBM-55S effectively inhibits the proliferation of cancer cells by inducing cell cycle arrest and apoptosis. MBM-55S shows antitumor activities, and no obvious toxicity to mice[1].
SU16f is a potent and selective PDGFRβ inhibitor with IC50s of 10 nM, 140 nM, 2.29 μM for PDGFRβ, PDGFR1, PDGFR2, respectively[1]. Neutralization of PDGFRβ receptor by SU16f blocks the promoting role of GC-MSCs (gastric cancer-derived mesenchymal stem cells) conditioned medium in gastric cancer cell proliferation and migration[2].
TGFβRI-IN-2 (compound 18) is a potent, selective and orally active (Activin-Like Kinase 5) ALK 5 inhibitor with pIC50 and pEC50 values of 7.6 and 6.63, respectively. TGFβRI-IN-2 can produce observed cardiac toxicity in vivo at high dose[1].
MSDC-0602K (Azemiglitazone potassium), a PPARγ-sparing thiazolidinedione (Ps-TZD), binds to PPARγ with the IC50 of 18.25 μM[1]. MSDC-0602K modulates the mitochondrial pyruvate carrier (MPC). MSDC-0602K can be used for the research of fatty liver including dysfunctional lipid metabolism, inflammation, and insulin resistance[2]. MSDC-0602K, an insulin sensitizer, improves insulinemia and fatty liver disease in mice, alone and in combination with Liraglutide[3].
FLT3-IN-15 is a highly potent and orally active FLT3 inhibitor with IC50s of 0.87 nM and 0.32 nM for FLT3 and FLT3/D835Y, respectively. FLT3-IN-15 can be used for researching acute myeloid leukemia[1].
Insulin (swine) is a porcine-derived insulin used in diabetes research[1].
BCR-ABL-IN-2 is an inhibitor of BCR-ABL1 tyrosine kinase, with IC50s of 57 nM, 773 nm for ABL1native and ABL1T315I, respectively.
Pinealon is a 3-amino acid peptide and shows neuroprotective properties. Pinealon prevents reactive oxygenspecies (ROS) accumulation and supressesthe activation of ERK 1/2. Pinealon has the ability to stimulate the functional activity of the main cellular elements of brain tissue, reduce the level of spontaneous cell death. Pinealon protects the rat offspring from prenatal hyperhomocysteinemia[1][2][3].
BCR-ABL-IN-5 (compound II) is a Bcr-Abl kinase (Breakpoint cluster region-Abelson) inhibitor. BCR-ABL-IN-5 inhibits Bcr-AblWT and Bcr-AblT3151 with the IC50 value of 0.014 μM and 0.45 μM, respectively. BCR-ABL-IN-5 has some anti-proliferative activity against leukemic cells[1].
NVP-BVU972 is a selective and potent Met inhibitor (IC50 = 14 nM). Antitumor agents.IC50 value: 14 nM [1]Target: MetNVP-BVU972 potently inhibits MET kinase but displays low inhibition against other kinases including the most closely related kinase RON with IC50 values of more than 1000 nM. NVP-BVU972 also suppresses constitutive MET phosphorylation in GTL-16 cells or HGF-stimulated MET phosphorylation in A549 cells with IC50 values of 7.3 nM and 22 nM, respectively. NVP-BVU972 potently prevents the growth of the MET gene amplified cell lines GTL-16, MKN-45 and EBC-1 with IC50 values of 66 nM, 82 nM and 32 nM, respectively. In line with their high frequency in the NVP-BVU972 screen, Y1230 and D1228 mutations give rise to dramatic shifts in the measured IC50 values for NVP-BVU972 in BaF3 cell line. Resistance triggered by V1155L is more limited to NVP-BVU972. A dose-dependent reduction in TPR-MET phosphorylation when applying NVP-BVU972 to BaF3 cells expressing wild-type TPR-MET. Both Y1230H and D1228A mutations abrogated the effect of NVP-BVU972 but not AMG 458. However, F1200I and L1195V interferes with the potency of NVP-BVU972 to prevent TPR-MET phosphorylation.
Amuvatinib hydrochloride (MP470 hydrochloride) is a multi-targeted receptor tyrosine kinases inhibitor, which inhibits c-Kit (D816V), c-Kit (D816H), c-Kit (V560G), c-Kit (V654A), PDGFRα (D842V), and PDGFRα (V561D) with IC50s of 950 nM, 10 nM, 34 nM, 127 nM, 81 nM, and 40 nM, respectively[1]. Antineoplastic activity[2].
Capmatinib (INC280; INCB28060) hydrochloride is a potent, orally active, selective, and ATP competitive c-Met kinase inhibitor (IC50=0.13 nM). Capmatinib hydrochloride can inhibit phosphorylation of c-MET as well as c-MET pathway downstream effectors such as ERK1/2, AKT, FAK, GAB1, and STAT3/5. Capmatinib hydrochloride potently inhibits c-MET-dependent tumor cell proliferation and migration and effectively induces apoptosis. Antitumor activity. Capmatinib hydrochloride is largely metabolized by CYP3A4 and aldehyde oxidase[1][2][3].
ALK-IN-26 is an ALK inhibitor with IC50 value of 7.0 μM for ALK tyrosine kinase. ALK-IN-26 has good pharmacokinetic properties and blood-brain barrier (BBB) permeability. ALK-IN-26 can induce apoptosis, autophagy and necrosis. ALK-IN-26 can be used in glioblastoma studies[1].
hTrkA-IN-1 is a potent and orally active inhibitor of TrkA kinase with an IC50 of 1.3 nM, compound 2. extracted from patent WO2015175788. hTrkA-IN-1 can be used for the study of inflammatory disease, such as prostatitis, pelvic, et al[1].