src inhibitor-3

Src Inhibitor 3 is an effective inhibitor of c-terminal Src kinase (IC50 <3 nM in CSK HTRF, <4 nM in Caliper assay). Src Inhibitor 3 increases T cell proliferation induced by T cell receptor signaling.

SI-2 is an inhibitor (SMI) of steroid receptor coactivator-3 (SRC-3 or AIB1). SI-2 can selectively reduce the transcriptional activities and the protein concentrations of SRC-3 in cells, and selectively induce breast cancer cell death with IC50 values in the low nanomolar range (3-20 nM), but not affect normal cell viability.

CCT241161 is an orally active pan-RAF inhibitor, with IC50 values of 3, 6, 10, 15, and 30 nM for LCK, CRAF, SRC, V600E-BRAF, and BRAF, respectively. It exhibits significant activity against BRAF and NRAS mutant melanomas and demonstrates anticancer cell proliferative effects [1].

A 419259 trihydrochloride (RK 20449 trihydrochloride) is an Src family kinases inhibitor (IC50s: 9 nM, 3 nM and 3 nM for Src, Lck and Lyn).

DCC-2036 (Rebastinib (DCC-2036)) is a conformational control Bcr-Abl inhibitor for Abl1(WT, IC50: 0.8 nM) and Abl1(T315I, IC50: 4 nM), also inhibits LYN, SRC, HCK, FGR, FLT3, KDR, and Tie-2, and low activity to c-Kit. Rebastinib aimed at the Angiopoietin2-Tie2 pathway.

GW 5074 (Raf1 Kinase Inhibitor I)(IC50=9 nM) is an effective and specific c-Raf inhibitor. It has no effect on the activities of JNK1 2 3, MEK1, MKK6 7, CDK1 2, c-Src, p38 MAP, VEGFR2 or c-Fms.

WYE-687 is an ATP-competitive and selective inhibitor of mTOR with an IC50 of 7 nM; it blocks mTORC1 pS6K(T389) and mTORC2 P-AKT(S473) without affecting P-AKT(T308). Its selectivity for mTOR is greater than PI3Kα (>100-fold) and PI3Kγ (>500-fold).

(E)-SI-2 is a potent small-molecule inhibitor of steroid receptor coactivator-3 (SRC-3 or AIB1) that can selectively inhibit the intrinsic transcriptional activities of SRC-3, also inhibits SRC-1 and SRC-2. It selectively reduces cellular protein levels of SRC-3, but not that of CARM-1, blocks MDA-MB-468 cell growth with an IC50 value of 3.4 nM, but spares normal cells.

A-419259 (RK-20449) is an apoptosis inducer that selectively inhibits the Src family of kinases, including Src,LCK, and Lyn, with an IC50=3 to 9 nM.

SI-2 hydrochloride (EPH 116 hydrochloride) is a highly promising inhibitor of SRC-3 SMI: SRC-3 (PPI)(IC50 values of 3-20 nM for breast cancer cell death), with acceptable oral availability.

5Z-7-Oxozeaenol (FR148083) is a potent, irreversible and selective inhibitor of transforming growth factor (TGF)-β-activated kinase 1 with IC50 of 8.1 nM for TAK1 and low activity against MEK1 with IC50 of 411 nM, it is also an inhibitor of VEGF-R2 with IC50 of 52 nM.

Tandutinib (CT53518) (MLN518, CT53518), an effective FLT3 antagonist (IC50: 0.22 μM), can also inhibit c-Kit and PDGFR, 15-20 fold higher potency for FLT3 versus CSF-1R and >100-fold selectivity for the same target versus FGFR, EGFR, and KDR.

Rigosertib (ON-01910) is a selective, non-ATP-competitive PLK1 inhibitor (IC50: 9 nM) and multi-kinase inhibitor. As a selective anti-cancer agent, Rigosertib induces apoptosis by inhibiting the PI3 kinase Akt pathway, promotes histone H2AX phosphorylation, and induces G2 M arrest in the cell cycle.

Protein kinase inhibitor 11 (Compound I-96) is an agent that inhibits the activity of PIM-1, CDK-2, GSK-3, and SRC. It shows potential for research in cancer, autoimmune diseases, and neurodegenerative disorders.

TGF-βRI inhibitor 3 (Compound 9ac) is a selective inhibitor of TGF-β that effectively suppresses the TGF-β signaling pathway. It exhibits IC50 values of 13 μM for c-Src kinase and 0.63 μM for ALK5 kinase.

Protein kinase inhibitor 13 (Compound I-90) functions as a kinase inhibitor, specifically targeting kinases such as PIM-1, CDK-2, GSK-3, and SRC.

PP 3 is a Negative control for the Src kinase inhibitor PP 2

KW-2449 is a multiple-targeted inhibitor, mostly for Flt3 (IC50: 6.6 nM), modestly effective to Bcr-Abl, FGFR1, and Aurora A; little inhibitory on PDGFRβ, IGF-1R, EGFR.

ENMD-2076, a multi-targeted kinase inhibitor, has specific activity against Aurora A, Flt3, KDR VEGFR2, Flt4 VEGFR3, FGFR1, FGFR2, Src, PDGFRα.

CHIR-98014 (CT98014) is a selective GSK3 inhibitor; potentiate insulin activation of glucose transport and utilization in vitro and in vivo.

PKC412(Midostaurin (PKC412); CGP41231; CGP41251) is a broad spectrum protein kinase inhibitor. Midostaurin inhibits protein kinase C alpha (PKCalpha), vascular endothelial growth factor receptor 2 (VEGFR2), c-kit, platelet-derived growth factor receptor (PDGFR) and FMS-like tyrosine kinase 3 (FLT3) tyrosine kinases, which may result in disruption of the cell cycle, inhibition of proliferation, apoptosis, and inhibition of angiogenesis in susceptible tumors.

Tpl2 kinase inhibitor is an inhibitor of tumor progression locus 2 (Tpl2; IC50= 0.05 μM).1It is selective for Tpl2 over MEK, p38 MAPK, Src, MK2, and PKC (IC50s = >40, 180, >400, 110, and >400 μM, respectively). Tpl2 kinase inhibitor inhibits LPS-induced TNF-α production in isolated human monocytes and whole blood (IC50s = 0.7 and 8.5 μM, respectively). It enhances differentiation induced by calcitriol in HL-60 and U937 leukemia cells when used at a concentration of 5 μM.2Tpl2 kinase inhibitor (5 μM) inhibits the proliferation of KG-1a leukemia cells.3 1.Garvin, L.K., Green, N., Hu, Y., et al.Inhibition of Tpl2 kinase and TNF-α production with 1,7-naphthyridine-3-carbonitriles: Synthesis and structure-activity relationshipsBioor. Med. Chem. Lett.15(23)5288-5292(2005) 2.Wang, X., and Studzinski, G.P.Expression of MAP3 kinase COT1 is up-regulated by 1,25-dihydroxyvitamin D3 in parallel with activated c-jun during differentiation of human myeloid leukemia cellsJ. Steroid. Biochem. Mol. Biol.121(1-2)395-398(2010) 3.Wang, X., Gocek, E., Novik, V., et al.Inhibition of Cot1/Tlp2 oncogene in AML cells reduces ERK5 activation and up-regulates p27Kip1 concomitant with enhancement of differentiation and cell cycle arrest induced by silibinin and 1,25-dihydroxyvitamin D3Cell Cycle9(22)4542-4551(2010)

SM1-71 is a potent multi-targeted acrylamide-modified TAK1 inhibitor that inhibits MKNK2, MAP2K1 2 3 4 6 7, GAK, AAK1, BMP2K, MAP3K7, MAPKAPK5, GSK3A B, MAPK1 3, SRC, YES1, FGFR1, ZAK (MLTK), MAP3K1, LIMK1 and RSK2.SM1-71 can be used as a kinase probe with anticancer activity and inhibits the proliferation of various cancer cell lines.

NG 25 is a type II kinase inhibitor that inhibits MAP4K2 and TAK1 (IC50s = 21.7 and 149 nM, respectively).1It also inhibits the Src family kinases Src and LYN (IC50s = 113 and 12.9 nM, respectively) and Abl family kinases (IC50s = 75.2 nM), as well as CSK, FER, and p38α (IC50s = 56.4, 82.3, and 102 nM, respectively). NG 25 (100 nM) prevents TNF-α-induced IKKα/β phosphorylation and IκB-α degradation in L929 cells. It inhibits secretion of IFN-α and IFN-β induced by CpG type B and CL097, respectively, in Gen2.2 cells in a concentration-dependent manner.2NG 25 decreases cell viability of HCT116KRASWT, and to a greater degree of HCT116KRASG13D, colorectal cancer cells in a concentration-dependent manner.3It also reduces tumor growth and increases the number of TUNEL-positive tumor cells in a CT26KRASG12Dmouse orthotopic model of colorectal cancer. 1.Tan, L., Nomanbhoy, T., Gurbani, D., et al.Discovery of type II inhibitors of TGFβ-activated kinase 1 (TAK1) and mitogen-activated protein kinase kinase kinase kinase 2 (MAP4K2)J. Med. Chem.58(1)183-196(2015) 2.Pauls, E., Shpiro, N., Peggie, M., et al.Essential role for IKKβ in production of type 1 interferons by plasmacytoid dendritic cellsJ. Biol. Chem. 287(23)19216-19228(2012) 3.Ma, Q., Gu, L., Liao, S., et al.NG25, a novel inhibitor of TAK1, suppresses KRAS-mutant colorectal cancer growth in vitro and in vivoApoptosis24(1-2)83-94(2019)