Tyrosine Kinases

Selitrectinib (LOXO-195) is a potent and selective inhibitor of the receptor tyrosine kinases(TRK)( TrkA and TrkC with IC50s of 0.6 and <2.5 nM, respectively)

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.

Pazopanib (GW786034), a small molecule inhibitor, inhibits multiple protein tyrosine kinases with potential antineoplastic activity. Pazopanib selectively inhibits VEGFR-1, -2 and -3, c-kit and PDGF-R, which may result in inhibition of angiogenesis in tumors in which these receptors are upregulated.

CP-547632 is an orally available and potent, ATP-competitive dual inhibitor of VEGFR-2 and FGF kinase F with IC50s of 11 nM and 9 nM, respectively. CP-547632 is selective, with higher selectivity for VEGFR2 and bFGF than for EGFR, PDGFRβ and related tyrosine kinases (TKs). PDGFRβ and related tyrosine kinases (TKs) CP-547632 has antitumour activity.

LCB 03-0110 Dihydrochloride is a potent inhibitor of the c-Src kinase (IC50 = 1.3 nM) and tyrosine kinases in the BTK and SYK family, as well as in the DDR2 family. It inhibits LPS-induced activation of macrophages and TGF-β1-induced activation of fibroblasts in vitro, inhibits activation of macrophages and fibroblasts, and inhibits scarring in wound healing models.

LCB 03-0110 (3-(2-(3-(Morpholinomethyl)phenyl)thieno[3,2-b]pyridin-7-ylamino)phenol) is a potent inhibitor of discoidin domain receptor family tyrosine kinases and strongly inhibits several tyrosine kinases, including the c-Src family, spleen tyrosine kinase, Bruton's tyrosine kinase, and vascular endothelial growth factor receptor 2, which are important for immune cell signaling and inflammatory reactions.

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).

KW-2450 free base is an orally bioavailable inhibitor of insulin-like growth factor 1 receptor (IGF-1R) and insulin receptor (IR) tyrosine kinases with potential antineoplastic activity. IGF-1R/IR inhibitor KW-2450 free base selectively binds to and inhibits the activities of IGF-1R and IR, which may result in the inhibition of tumor cell proliferation and the induction of tumor cell apoptosis. IGF-R1 and IR tyrosine kinases, overexpressed in a variety of human cancers, play significant roles in the stimulation of cellular proliferation, oncogenic transformation, and suppression of apoptosis.

Vitamin K2 (Menatetrenone) is a menaquinone compound and form of vitamin K2 with potential antineoplastic activity. Menatetrenone may act by modulating the signaling of certain tyrosine kinases, thereby affecting several transcription factors including c-myc and c-fos. This agent inhibits tumor cell growth by inducing apoptosis and cell cycle arrest.

N-phenylthiophene-2-carboximidamide is a thiophene derivative that functions as an inhibitor of protein tyrosine kinases (PTKs) and a ligand for G protein-coupled receptors (GPCRs).

Epidermal Growth Factor Receptor Peptide Acetate (Epidermal Growth Factor Receptor Peptide Acetate(96249-43-3 Free base)) exists on the cell surface and is activated by the binding of its specific ligands.EGFR belongs to the ErbB family of receptor tyrosine kinases (RTK).

(Rac)-SAR131675 is an effective and specific VEGFR-3 inhibitor. It inhibited VEGFR-3 tyrosine kinase activity (IC50: 20 nmol L) and VEGFR-3 autophosphorylation (IC50: 45 nmol L) in HEK cells, respectively. SAR131675 is highly specific for VEGFR-3 versus 107 receptors, enzymes, ion channels, and 65 kinases. SAR131675 is a highly specific VEGFR-3-TK inhibitor with significant antitumoral and antimetastatic activities in vivo through inhibition of lymphangiogenesis and TAM invasion.

TG 100572 Hydrochloride is a inhibitor of multi-targeted kinase which inhibits receptor tyrosine kinases and Src kinases(IC50s of 2, 7, 2, 16, 13, 5, 0.5, 6, 0.1, 0.4, 1, 0.2 nM for VEGFR1, VEGFR2, FGFR1, FGFR2, PDGFRβ, Fgr, Fyn, Hck, Lck, Lyn, Src, Yes, respectively).

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

SB1317 (TG02) is a potent inhibitor of cyclin dependant kinases (CDKs), Janus kinase 2 (JAK2), and Fms-like tyrosine kinase-3 (FLT3).

Pyridone 6 (JAK Inhibitor)(CMP 6) is a potent and selective inhibitor of JAK1 (IC50=15 nM, murine JAK1), JAK2 (IC50=1 nM), JAK3 (Ki=5 nM), and Tyk2 (IC50=1 nM); displaying significantly weaker affinities (130 nM to 10 mM) for other protein tyrosine kinases.

Dasatinib monohydrate (BMS-354825 Monohydrate) is an orally bioavailable synthetic small molecule-inhibitor of SRC-family protein-tyrosine kinases. Dasatinib monohydrate binds to and inhibits the growth-promoting activities of these kinases. Apparently, because of its less stringent binding affinity for the BCR-ABL kinase, Dasatinib monohydrate has been shown to overcome the resistance to imatinib of chronic myeloid leukemia (CML) cells harboring BCR-ABL kinase domain point mutations.

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

LFM-A13（IC50=2.5 μM）, a specific Bruton's tyrosine kinase (BTK), is more than 100-fold specificity than other protein kinases, such as JAK1, JAK2, HCK, EGFR, and IRK.

Lorlatinib (PF-6463922) is an orally available, ATP-competitive inhibitor of the receptor tyrosine kinases, anaplastic lymphoma kinase (ALK) and C-ros oncogene 1 (Ros1), with potential antineoplastic activity.

Piceatannol (Astringenin) is an anti-inflammatory, immunomodulatory and antiproliferative agent. It inhibits p56lck and syk protein tyrosine kinases and inhibits NF-κB activation and gene expression of TNF-induced. It is synthetic from the conversion of resveratrol by cytochrome P450 1B1.

Crizotinib (PF-02341066) is an ATP-competitive small-molecule tyrosine kinases inhibitor of c-MET (IC50: 8 nM) and ALK (IC50: 20 nM) receptor.

Anlotinib is an orally available inhibitor of multiple tyrosine kinases, including human VEGFR1, VEGFR2, VEGFR3, PDGFRβ, and c-Kit with IC50 values of 26.9, 0.2, 0.7, 115, and 14.8 nM, respectively. It demonstrates selectivity for these targets over others like c-Met, c-Src, HER2, and EGFR, which have IC50 values of >2,000 nM. Additionally, anlotinib effectively inhibits FGFR1 with an IC50 of 11.7 nM. Its anti-tumor activity has been confirmed in various cancer cell lines, including colorectal, renal, lung, breast, leukemia, melanoma, and glioblastoma, with IC50s ranging from 3-12.5 μM. Anlotinib also inhibits VEGF-induced endothelial cell migration (IC50= 0.1 nM) and FBS-induced tube formation, contributing to its anti-angiogenic effects. In vivo, it showed a significant reduction in tumor volume and angiogenesis in a SW620 xenograft mouse model at a dose of 3 mg/kg per day, highlighting its potential for cancer therapy.

JNJ-38158471 (CS-2660), a highly selective, orally available, well tolerated VEGFR2 inhibitor with IC50 of 40 nM, inhibits closely related tyrosine kinases such as Ret and Kit with IC50 of 180 nM and 500 nM.

ACC-789 (NVP-ACC789 (ZK202650); ZK-202650) is an effective, specific and orally active inhibitor of the VEGF receptor tyrosine kinases.

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.

Oxindole (Indolin-2-one) is an aromatic heterocyclic building block. 2-indolinone derivatives have become lead compounds in the research of kinase inhibitors.Oxindole structure has been used in receptor tyrosine kinases (RTKs) inhibitors such as SU4984 and intedanib, the RTK family represents an important therapeutic target for anti-cancer drug development.

ROS kinases-IN-1 is a ROS tyrosine kinase inhibitor with IC50 value of 1.22 μM. ROS kinases-IN-1 shows anti-tumor activity.

AD57, as polypharmacological cancer therapeutic, is designed to regulate multiple targets related to cancer blocks the receptor tyrosine kinase RET in Drosophila (IC50: 2 nM). AD57 effectively suppresses tyrosine kinase RET, weakens the activity of numero

Tyrphostin AG30 (AG30) (AG30) is a potent protein tyrosine kinases (PTK) inhibitor.

MGCD-265 analog (Glesatinib) is an orally bioavailable multitargeted tyrosine kinase inhibitor with potential antineoplastic activity with IC50 of 29 nM and 10 nM for c-Met and VEGFR2, respectively.

Sorafenib N-oxide is an active metabolite of sorafenib , an inhibitor of Raf-1, B-RAF, and receptor tyrosine kinases. Sorafenib N-oxide inhibits FLT3 that contains the internal tandem duplication mutation (FLT3-ITD; Kd = 70 nM) and inhibits proliferation of MV4-11 acute myeloid leukemia (AML) cells expressing FLT3-ITD (IC50 = 25.8 nM). It is selective for AML cell lines containing FLT3-ITD over lines containing wild-type FLT3 (IC50s = 3.9-13.3 μM). Sorafenib N-oxide is also a linear-mixed inhibitor of the cytochrome P450 (CYP) isoform CYP3A4 (Ki = 15 μM in human liver microsomes).

Imatinib D8 is a deuterium-labeled Imatinib. Imatinib is an orally bioavailable tyrosine kinases inhibitor that inhibits BCR/ABL, PDGFR, v-Abl, and c-kit kinase activity.

Son of sevenless homolog 1 (Sos1) is a guanine nucleotide exchange factor (GEF) that directs the exchange of Ras-GDP to Ras-GTP by binding to SH3 domains of the growth factor receptor-bound protein 2 (Grb2), leading to the activation of ERK. Ras inhibitory peptide is a synthetic peptide that contains the sequence PVPPR, which corresponds to a region within human Sos1 that interacts with an SH3 domain of Grb2. It specifically blocks the interaction of the GEF with Grb2, preventing an interaction that is essential for Ras activation by receptor tyrosine kinases, including epidermal growth factor receptor.

TG 100572 is a inhibitor of multi-targeted kinase which inhibits receptor tyrosine kinases and Src kinases(IC50s of 2, 7, 2, 16, 13, 5, 0.5, 6, 0.1, 0.4, 1, 0.2 nM for VEGFR1, VEGFR2, FGFR1, FGFR2, PDGFRβ, Fgr, Fyn, Hck, Lck, Lyn, Src, Yes, respectively).

SU14813 maleate is an inhibitor of multi-targeted receptor tyrosine kinases (IC50s: 2, 50, 4, 15 nM for VEGFR1, VEGFR2, PDGFRβ, and KIT).

KBP-7018 is a potent, selective tyrosine kinase inhibitor with effects on three fibrotic kinases c-KIT, RET, and PDGFR (IC50 values are 10nM, 7.6 nM and 25nM respectively).

LY2457546 is a potent and orally bioavailable inhibitor of multiple receptor tyrosine kinases involved in angiogenic and tumorigenic signalling. LY2457546 demonstrates potent activity against targets that include VEGFR2 (KDR), PDGFRβ, FLT-3, Tie-2 and members of the Eph family of receptors. In vivo, LY2457546 inhibited VEGF-driven autophosphorylation of lung KDR in the mouse and rat in a dose and concentration dependent manner. LY2457546 was well tolerated and exhibited efficacy in a 13762 syngeneic rat mammary tumor models. Additionally, LY2457546 caused complete regression of well-established tumors in an acute myelogenous leukemia (AML) FLT3-ITD mutant xenograft tumor model. The unique spectrum of target activity, potent in vivo anti-tumor efficacy in a variety of rodent and human solid tumor models, exquisite potency against a clinically relevant model of AML, and non-clinical safety profile justify the advancement of LY2457546 into clinical testing. (source: Invest New D......

PF-184 is a potent, selective inhibitor of IKK-2 with an IC50 value of 37 nM, demonstrating significant selectivity over rhIKK-1, IKKi, and over 30 other tyrosine and serine/threonine kinases. It is utilized in inflammation research, including studies on asthma and chronic obstructive pulmonary disease.

Imatinib Impurity E is a specific impurity found in Imatinib, an orally available inhibitor of multiple tyrosine kinases, including BCR/ABL, v-Abl, PDGFR, and c-kit. Imatinib (STI571) operates by semi-competitively inhibiting enzyme activity; it binds adjacent to the ATP binding site, inducing a closed or self-inhibited conformation [1] [2] [3] [4]. Additionally, Imatinib acts as an inhibitor against SARS-CoV and MERS-CoV [5].

Lestaurtinib is a multi-kinase inhibitor. It also has effective activity against the Trk family of receptor tyrosine kinases. Lestaurtinib inhibits JAK2, FLT3, and TrkA (IC50s: 0.9, 3, and less than 25 nM).

DW532 is one of simplified analogues of hematoxylin that has shown broad-spectrum inhibition on tyrosine kinases and in vitro anti-cancer activities. DW532 inhibited EGFR and VEGFR2 in vitro kinase activity (the IC50 values were 4.9 and 5.5 μmol/L, respectively), and suppressed their downstream signaling. DW532 dose-dependently inhibited tubulin polymerization via direct binding to tubulin, thus disrupting the mitotic spindle assembly and leading to abnormal cell division. In a panel of human cancer cells, DW532 (1 and 10 μmol/L) induced G2/M phase arrest and cell apoptosis, which subsequently resulted in cytotoxicity. Knockdown of BubR1 or Mps1, the two core proteins of the spindle assembly checkpoint dramatically decreased DW532-induced cell cycle arrest in MDA-MB-468 cells. Moreover, treatment with DW532 potently and dose-dependently suppressed angiogenesis in vitro and in vivo. ( Acta Pharmacol Sin. 2014 Jul;35(7):916-28.)

GW 441756 is a specific Tropomyosin-related kinase A (TrkA) inhibitor with an IC50 value of 2 nM.

Imatinib D4 is a deuterium-labeled Imatinib. Imatinib is an orally bioavailable tyrosine kinases inhibitor that selectively inhibits BCR/ABL, PDGFR, v-Abl, and c-kit kinase activity.

GSK2646264 (Compound 44) is a highly effective and specific inhibitor of spleen tyrosine kinase (SYK) with a pIC50 of 7.1. In addition to targeting SYK, GSK2646264 also inhibits several other kinases, including LCK, LRRK2, GSK3β, JAK2, VEGFR2, Aurora B, and Aurora A, with pIC50 values of 5.4, 5.4, 5.3, 5, 4.5, <4.6 and <4.3, respectively. Notably, GSK2646264 demonstrates skin penetrability, reaching both the epidermis and dermis [1].

Bosutinib hydrate (SKI-606 hydrate) is an orally active and potent dual kinase inhibitor of BCR-ABL and Src tyrosine kinases for the study of Philadelphia Chromosome Positive Chronic Granulocytic Leukemia.

Su1498 (Tyrphostin SU 1498) is a selective inhibitor of the receptor tyrosine kinase VEGF receptor 2 (VEGFR2, aka FLK1; IC50 = 700 nM), having negligible activity at several other serine/threonine and tyrosine kinases.1, 2 It effectively blocks signaling through VEGFR2 both in vitro and in vivo.1, 3 SU 1498 is used to study the role of VEGFR2 signaling in diverse processes, including angiogenesis, tumor growth, neural progenitor cell survival, and neuroregeneration.

Tyrphostin AG1433 (AG1433) is an inhibitor of tyrosine kinases and also a dual inhibitor of PDGFRβ(IC50s = 5.0 μM) and VEGFR-2 (Flk-1/KDR)(IC50s = 9.3 μM).

BVB-808 is a selective Jak2 type 1 inhibitor. Janus kinases are critical components of signaling pathways that regulate hematopoiesis. Mutations of the non-receptor tyrosine kinase JAK2 are found in many BCR-ABL-negative myeloproliferative neoplasms. Preclinical results support that JAK2 inhibitors could show efficacy in treating chronic myeloproliferative neoplasms. JAK2 has also been postulated to play a role in BCR-ABL signal transduction. Therefore, inhibitors of JAK2 kinases are turning into therapeutic strategies for treatment of chronic myelogenous leukemia (CML).

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.