cluster of differentiation antigen 135

Sorafenib (Bay 43-9006) is a multikinase inhibitor that inhibits Raf-1, B-Raf, VEGFR2, VEGFR3, VEGFR4, PDGFRβ, FLT3, c-Kit, and others (IC50=6/22/90/15/20/20/57/58 nM) with oral activity. Sorafenib has antitumor activity and can induce autophagy and apoptosis as well as agonistic ferroptosis.

Quizartinib (AC220) is an inhibitor of FLT3 (Kd: 1.6 nM) and demonstrates high selectivity for FLT3 when tested against a panel of 227 additional kinases.

Cabozantinib (XL184) is a multi-targeted tyrosine kinase receptor inhibitor that inhibits VEGFR2, c-Met, Kit, Axl, and Flt3 (IC50=0.035/1.3/4.6/7/11.3 nM). Cabozantinib exhibits both antitumor and antiangiogenic activity.

Gilteritinib (ASP2215) is a potent inhibitor at the FMS-related tyrosine kinase 3 (FLT3) and AXL tyrosine kinase receptors (IC50 = 0.29 nM and <1 nM, respectively). In preClinicalal studies, gilteritinib showed strong antileukemic and antitumor effects. Gilteritinib is currently in several Phase 3 Clinicalal trials for acute myeloid leukemia.

Cabozantinib hydrochloride (XL184) is a potent pan-tyrosine kinases inhibitor that inhibits VEGFR2, c-Met, Kit, Axl, and Flt4 (IC50s: 0.035, 1.3, 4.6, 7 and 6 nM).

4SC-203 is a multikinase inhibitor with potential antineoplastic activity. 4SC-203 selectively inhibits FMS-related tyrosine kinase 3 (FLT3/STK1), FLT3 mutated forms, and vascular endothelial growth factor receptors (VEGFRs).

AST 487 (NVP-AST 487) is a RET kinase inhibitor, inhibiting RET autophosphorylation and activation of downstream effectors. It also can inhibit Flt-3.

Sorafenib tosylate (Bay 43-9006) is a potent multikinase inhibitor (IC50s: 6/20/22 nM for Raf-1/VEGFR-3/B-Raf).

Pacritinib (SB1518) (SB1518) is an effective and specific inhibitor of JAK2 and FLT3 (IC50: 23/22 nM, in cell-free assays).

Amuvatinib (MP470) is an orally bioavailable synthetic carbothioamide with potential antineoplastic activity.

Sitravatinib (MGCD516) is an inhibitor targeting multiple RTKs involved in driving sarcoma cell growth, including c-Met, c-Kit, PDGFRα/β, PDGFR, and Axl.

R406 (R-406 besylate) is an effective Syk inhibitor (IC50: 41 nM) and shows no effects on Lyn.

Crenolanib (ARO 002) is an orally bioavailable type III tyrosine kinases inhibitor of PDGFRα/β and FLT3 (IC50s: 11, 3.2, and 4 nM).

FLT3-IN-3 is an effective FLT3 inhibitor, and the IC50s of FLT3 WT and FLT3 D835Y are 13 and 8 nM, respectively.

AT9283 (J-504568) is an effective multi-targeted inhibitor of JAK2(IC50=1.2 nM) and JAK3(IC50=1.1 nM), Aurora A, Aurora B and Abl(T315I).

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.

KG5 is a dual allosteric inhibitor of PDGFRβ and B-Raf with a Kd of 520 nM and 300 nM for PDGFRβ and PDGFRα. KG5 inhibits FLT3, KIT, and c-Raf with anticancer and antiangiogenic activities.

It is a tyrosine kinase inhibitor.

AC710 is a potent PDGFR inhibitor (Kds: 0.6, 1, 1.57, 1.3, 1 nM for FLT3, KIT, CSF1R, PDGFRα and PDGFRβ).

R406 free base (R406 (free base)) is a potent Syk inhibitor.

CCT241736 is an orally bioavailable dual FLT3/Aurora kinase inhibitor that also inhibits clinically relevant FLT3-resistant mutants including FLT3-ITD and FLT3, CCT241736, an advanced analog of CCT137690, is a preclinical development candidate for the treatment of human malignancies, and in particular AML in adults and children.

ATH686 is an potent and selective Inhibitor of FLT3.

UNC2025 (mrx-6313)(IC50 of 0.74 nM and 0.8 nM) is a potent and orally bioavailable dual MER/FLT3 inhibitor. UNC-2025 is about 20-fold selectivity higher than Axl and Tyro3.

Linifanib (AL-39324) (ABT-869) is a novel, potent ATP-competitive VEGFR/PDGFR inhibitor for KDR (IC50: 4 nM), CSF-1R (IC50: 3 nM), Flt-1/3 (IC50: 3/4 nM) and PDGFRβ (IC50: 66 nM). Linifanib may exhibit potent antiproliferative and apoptotic effects on tumor cells whose proliferation is dependent on mutant kinases, such as FMS-related tyrosine kinase receptor-3 (FLT3).

AMG 925 is a potent and orally bioavailable dual FLT3/CDK4 inhibitor with IC50 of 1 nM and 3 nM, respectively.

TG101209 is a selective JAK2 inhibitor with IC50 of 6 nM.

AZD2932 is a potent and multi-targeted kinase inhibitor VEGFR2, PDGFβ, Flt-3, and c-Kit.

LY2784544(Gandotinib (LY2784544)) is a potent JAK2 inhibitor (IC50: 3 nM), effective in JAK2V617F(Ki: 0.245 nM). The selectivity is higher 8- and 20-fold than JAK1 and JAK3.

PF 477736 (PF-736,PF-00477736) is a specifc, effective and ATP-competitive Chk1 inhibitor (Ki: 0.49 nM ) and also inhibits FGFR3, Aurora-A, VEGFR2, Flt3, Fms (CSF1R), Ret and Yes.

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

BPR1J-097) is a novel FLT-3 inhibitor(IC50: 11±7 nM) with promising in vivo anti-tumor activities. It also inhibits FLT-3 D835Y (IC50: 3 nM).

Altiratinib (DCC-2701)(DCC-2701) is a novel c-MET/TIE-2/VEGFR inhibitor; effectively reduce tumor burden in vivo and block c-MET pTyr(1349)-mediated signaling, cell growth and migration as compared with an HGF antagonist in vitro.

AKN-028 is an orally active and potent FLT3 tyrosine kinase inhibitor ( IC 50 = 6 nM). AKN-028 causes dose-dependent inhibition of FLT3 autophosphorylation.

G-749, a new-type FLT3 inhibitor, exhibits effective and sustained inhibition of the FLT3 wild type and mutants.

Ripretinib (DCC-2618) is an orally bioavailable inhibitor of KIT and PDGFRA.

1. Crotonoside (Isoguanosine) has much more active than adenosine in reducing the blood pressure in rabbits and cats, in decreasing the tone of isolated intestinal strips of the rabbit, guinea pig and hamster and in stimulating the isolated uterus of guinea pigs and hamsters. 2. Crotonoside inhibits the growth of S-18 and Ehrlich solid tumor in mice at the optimal doses of 96 mg/kg/day x 12 and 48 mg/kg/day x 12, with 1-T/C values of 65% and 6%, respectively.

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.

(E/Z)-Zotiraciclib ((E/Z)-TG02) inhibits CDK2, JAK2, and FLT3 effectively with IC50s of 13, 73, and 56 nM, respectively.

Tyrphostin AG1296 (Tyrphostin AG 1296) is an inhibitor of PDGFR with IC50 of 0.3-0.5 μM, no activity to EGFR.

MRX-2843 (UNC2371) is a potent and orally active inhibitor of MERTK and FLT3(IC50s of 1.3 nM and 0.64 nM, respectively).

Merestinib (LY2801653) is an orally available, small molecule inhibitor of the proto-oncogene c-Met (Ki: 2 nM) with potential antineoplastic activity. Merestinib electively binds to c-Met, thereby inhibiting c-Met phosphorylation and disrupting c-Met signal transduction pathways. This may induce cell death in tumor cells overexpressing c-Met protein or expressing the constitutively activated c-Met protein.

Dovitinib lactate hydrate (TKI258) is the Lactate of Dovitinib, which is a multitargeted RTK inhibitor, mostly for class III (FLT3/c-Kit) with IC50 of 1 nM/2 nM, also potent to class IV (FGFR1/3) and class V (VEGFR1-4) RTKs with IC50 of 8-13 nM, less potent to InsR, EGFR, c-Met, EphA2, Tie2, IGFR1 and HER2. Phase 4.

CHIR-124 is an effective Chk1 inhibitor (IC50: 0.3 nM). It has 2, 000-fold selectivity against Chk2, 500- to 5, 000-fold less activity against Cdc2 and CDK2/4.

FLT3-IN-2 is an FLT3 inhibitor (IC50<1 μM).

Fostamatinib Disodium (R788 Disodium) is an orally available Syk kinase inhibitor with potential anti-inflammatory and immunomodulating activities.

Dovitinib lactate (TKI-258 lactate)(TKI258) lactate is a potent inhibitor of fibroblast growth factor receptor 3 (FGFR3) (IC50 :5 nM).

Dovitinib (CHIR-258) (TKI258, CHIR258) is a multitargeted RTK inhibitor, mostly for class III (FLT3/c-Kit, IC50: 1/2 nM), also effective to class IV (FGFR1/3) and class V (VEGFR1-4) RTKs (IC50: 8-13 nM), less potent to EGFR, InsR, EphA2, c-Met, IGF-1R, Tie2, and HER2.

FN-1501 is a potent FLT3 and CDK inhibitor (IC50s: 2.47, 0.85, 1.96, and 0.28 nM for CDK2/cyclin A, CDK4/cyclin D1, CDK6/cyclin D1 and FLT3, respectively). FN-1501 also has anticancer activity.

Fostamatinib (R788)(IC50 of 41 nM), which is a prodrug of the active metabolite R406, is a Syk inhibitor. It does not work on Lyn.

TCS 359 (FLT3 Inhibitor) is a potent FLT3 inhibitor with IC50 of 42 nM.

Quizartinib, also know as AC220 and AC010220, is an orally available FLT3 / STK1 inhibitor with potential antineoplastic activity. Class III receptor tyrosine kinase inhibitor AC220 selectively inhibits class III receptor tyrosine kinases, including FMS-related tyrosine kinase 3 (FLT3/STK1), colony-stimulating factor 1 receptor (CSF1R/FMS), stem cell factor receptor (SCFR/KIT), and platelet derived growth factor receptors (PDGFRs), resulting in inhibition of ligand-independent leukemic cell proliferation and apoptosis. Mutations in FLT3, resulting in constitutive activation, are the most frequent genetic alterations in acute myeloid leukemia (AML) and occur in approximately one-third of AML cases.

Iso-guanosine derivative