PDGFRα/FLT3-ITD-IN-1 (Compound 12d) is a potent inhibitor of PDGFRα/FLT3 with IC50s of more than 0.036 and 0.003 μM, respectively. PDGFRα/FLT3-ITD-IN-1 has the potential for the research of acute myeloid leukemia or chronic eosinophilic leukemia[1].
CHMFL-BMX-078 is a highly potent and selective type II irreversible BMX kinase inhibitor with an IC50 of 11 nM.
KLTWQELYQLKYKGI (QK) is a VEGF mimicking peptide, binds to the VEGF receptors and competes with VEGF. KLTWQELYQLKYKGI is active in gastric ulcer healing in rodents when administered either orally or systemically. KLTWQELYQLKYKGI shows the ability to induce capillary formation and organization in vitro[1].
NVP-ADW742(ADW742; GSK 552602A ) is an selective IGF-1R inhibitor with IC50 of 0.17 μM, >16-fold more potent against IGF-1R than InsR; little activity to HER2, PDGFR, VEGFR-2, Bcr-Abl and c-Kit.IC50 value: 0.17 uM [1]Target: IGF-1Rin vitro: NVP-ADW742 exhibits a 6-fold greater selectivity for IGF-1R versus InsR with IC50 of 2.8 μM; minimal inhibitory activity against c-Kit, HER1, PDGFR, VEGFR2, or Bcr-Abl p210 with IC50 greater than 5 μM. NVP-ADW742 significantly inhibits the serum-stimulated cell proliferation in a variety of tumor cell lines in dose-dependent manner, with IC50 values of 0.1-0.5 μM for the multiple myeloma (MM) cell lines, and the antitumor effects on MM cells can not be overcome by the co-culture with BMSCs. NVP-ADW742 also abrogates the responsiveness of tumor cells to IL-6 in the presence of serum [1]. Pretreatment of the H526 cell line with NVP-ADW742 inhibited IGF-IR signaling and growth with IC(50) values between 0.1 and 0.4 micro M [2].in vivo: Administration of NVP-ADW742 at 10 mg/kg twice daily significantly inhibits tumor growth, prolongs survival, and enhances the antitumor effect of cytotoxic chemotherapy melphalan in the mice model of diffuse MM [1].
Gunagratinib (ICP-192) is a low toxicity and orally active pan-FGFR (fibroblast growth factor receptors) inhibitor that potently and selectively inhibits FGFR activities irreversibly by covalent binding. Gunagratinib can be used for the research of cancer[1].
GNF-5, an analogue of GNF-2 with improved pharmacokinetic properties, is a selective non-ATP competitive inhibitor of Bcr-Abl with an IC50 value of 0.22±0.1 uM (Wild type Abl).IC50 Value: 0.22±0.1 uM (Wild type Abl) [1]Target: Abl GNF-5 is a cell-permeable GNF-2 N-hydroxyethyl carboxamide analog that exhibits in vivo efficacy in suppressing the proliferation of Bcr-abl-expressing Ba/F3 (93% and 83% of no-treatment control, respectively, on days 5 and 7 post treatment; 100 mg/kg b.i.d.) and bone marrow cells (~75% of no-treatment control in both WBC counts and spleen weight on day 7 post treatment; 50 mg/kg b.i.d.) in murine xenograft models of leukemia. Similar to GNF-2, GNF-5 exerts its effect via an allosteric mechanism (IC50 = 0.22 M against wild-type Abl) by targeting the myristate-binding pocket near the c-terminus of Abl kinase domain and thereby altering the conformational dynamics of the ATP-binding pocket. GNF-5 is ineffective toward the myristate-binding site mutant E505K and the ATP-binding site 'gatekeeper' mutant T315I.
EGFR-IN-28 is a potent EGFR inhibitor. EGFR-IN-28 has antitumor activity[1].
UNC2541 is a potent and Mer tyrosine kinase (MerTK)-specific inhibitor, binds in the MerTK ATP pocket, with an IC50 of 4.4 nM, more selective over Axl, Tyro3 and Flt3. UNC2541 inhibits phosphorylated MerTK (pMerTK; EC50, 510 nM)[1].
Patritumab (Human Anti-ERBB3 Recombinant Antibody) is a neutralizing monoclonal antibody to ERBB3. Patritumab shows a synergy with Cetuximab (HY-P9905), potently inhibits the phosphorylation of EGFR, HER2, HER3, ERK, and Akt. Patritumab also induces cell apoptosis and suppresses the growth of pancreatic, non-small cell lung cancer, and colorectal cancer xenograft tumors[1].
Glesatinib hydrochloride is an inhibitor of the MET and Axl receptor tyrosine kinase pathways, which drive tumour growth when altered.Target: MET, AxlGlesatinib is an orally bioavailable, small-molecule, multitargeted tyrosine kinase inhibitor with potential antineoplastic activity. MGCD265 binds to and inhibits the phosphorylation of several receptor tyrosine kinases (RTKs), including the c-Met receptor (hepatocyte growth factor receptor); the Tek/Tie-2 receptor; vascular endothelial growth factor receptor (VEGFR) types 1, 2, and 3; and the macrophage-stimulating 1 receptor (MST1R or RON). Glesatinib is a tyrosine kinase inhibitor that is expected to potently and selectively target tumors in patients with driver alterations in MET (mutations and gene amplification) and Axl (rearrangements) that occur in approximately 8% of patients with non-small cell lung cancer (NSCLC). Glesatinib is being evaluated in a Phase 1b study in patients with solid tumors that have genetic alterations in MET or AXL genes. The Phase 2 trial in NSCLC patients with MET genetic alterations is underway to confirm and extend the data that supports the clinical benefit of Glesatinib in patients with driver mutations in MET. Genetic alterations in these targets have been implicated as drivers of tumor growth and disease progression in NSCLC, gastroesophageal cancer and other solid tumors. MET and Axl are also implicated as drivers of tumor progression in patients whose tumors have become resistant to EGFR inhibitors. Therefore, Mirati believes that the combination of Glesatinib with an EGFR inhibitor could potentially treat patients who have become resistant to agents targeting EGFR. Mirati retains worldwide rights to Glesatinib.
CEP-37440 is a novel potent and selective Dual FAK/ALK inhibitor with IC50 s of 2.3 nM (FAK) and 120 nM(ALK cellular IC50 in 75% human plasma).IC50 value: 2.3 nM (FAK); 120 nM (ALK cellular IC50 in 75% human plasma)Target: Dual FAK/ALKPreparation of fused bicyclic 2,4-diaminopyrimidine derivatives as a dual ALK and FAK inhibitorBy Jacobs, Martin J.; Ott, Gregory R. From PCT Int. Appl. (2013), WO 2013134353 A1 20130912.
p60c-src substrate II is an efficient pentapeptide substrate for the tyrosine kinase pp60c-src[1].
AG-1024 (Tyrphostin) inhibits IGF-1R autophosphorylation with IC50 of 7 μM, less potent to IR with IC50 of 57 μM.IC50 value: 7 uM (IGF-1R autophosphorylation); 57 uM (IR) [1]Target: IGF-1R; IRin vitro: AG-1024 blocks the IGF-1 receptor and IR autophosphorylation with IC50 of 7 μM and 57 μM, respectively. AG-1024 also inhibits the receptor tyrosine kinase activity towards exogenous substrates (TKA) with IC50 values of 18 μM and 80 μM, respectively [1]. Human breast cancer cell line MCF-7 exposure to Tyrphostin AG 1024 inhibited proliferation and induced apoptosis in a time-dependent manner, and the degree of growth inhibition for IC20 plus irradiation (4 Gy) was up to 50% compared to the control. Examination of Tyrphostin AG 1024 effects on radiation response demonstrated a marked enhancement in radiosensitivity and amplification of radiation-induced apoptosis [2]. AG-1024 significantly inhibits melanoma cell proliferation with an IC50 of <50 nM in the absence of serum, by blocking MAPK/ERK2 signaling, subsequently rapidly inducing pRb dephosphorylation and activation, and eventually the formation of growth suppressive pRb-E2F complexes [3].in vivo: Administration of AG-1024 at a dose of 30 μg for 10 days significantly inhibits the tumor growth of Ba/F3-p210 xenograft in mice [4].
Afatinib (BIBW 2992) oxalate is an orally active, potent and irreversible dual specificity inhibitor of ErbB family (EGFR and HER2), with IC50 values of 0.5 nM, 0.4 nM, 10 nM and 14 nM for EGFRwt, EGFRL858R, EGFRL858R/T790M and HER2, respectively. Afatinib oxalate can be used for the research of esophageal squamous cell carcinoma (ESCC), non-small cell lung cancer (NSCLC) and gastric cancer[1][2][3][4].
Insulin(human) is a peptide hormone that regulates the level of sugar (glucose) in the blood and that is produced by the beta cells of the pancreatic islets.
PPY-A is a potent T315I mutant and wild-type Abl kinases inhibitor with IC50s of 9 and 20 nM, respectively. PPY-A inhibits Ba⁄F3 cells transformed with wild-type Abl and Abl T315I mutantl with IC50s of 390 and 180 nM, respectively. PPY-A can be used for the research of chronic myeloid leukemia (CML)[1].
Chrysotoxine is a dual inhibitor of Src/Akt. Chrysotoxine suppresses cancer stem cells (CSCs) phenotypes by down-regulating Src/Akt signaling. Chrysotoxine reduces cell viability and increases apoptosis level in H460 and H23 cells instead of non-tumor cell lines. Chrysotoxine shows rapid excretion and low bioavailability in rats. Chrysotoxine is used in cancer research[1][2].
EGFR mutant-IN-2 (Compound D51) is an EGFR mutant inhibitor. EGFR mutant-IN-2 inhibits the EGFRL858R/T790M/C797S mutant with an IC50 value of 14 nM. EGFR mutant-IN-2 inhibits the EGFRdel19/T790M/C797S mutant with an IC50 value of 62 nM. EGFR mutant-IN-2 has favorable PK parameters, safety properties, in vivo stability, and antitumor activity[1].
TL13-22 is a negative control for TL13-12 (HY-122582) and a potent ALK inhibitor with an IC50 of 0.54 nM. TL13-22 does not degrade ALK in cells[1].
SU4312 is the racemate of (Z)-SU4312 and (E)-SU4312. (Z)-SU4312 inhibits PDGFR and FLK-1 with IC50s of 19.4 and 0.8 μM, respectively. (E)-SU4312 inhibits PDGFR, FLK-1, EGFR, HER-2, and IGF-1R with IC50s of 24.2, 5.2, 18.5, 16.9 and 10.0 μM, respectively[1].
N-(p-Coumaroyl) Serotonin is a polyphenol isolated from the seeds of safflower and has antioxidative, anti-atherogenic and anti-inflammatory properties. N-(p-Coumaroyl) Serotonin inhibits PDGF-induced on phosphorylation of PDGF receptor and Ca2+ release from sarcoplasmic reticulum[1]. N-(p-Coumaroyl) Serotonin ameliorates atherosclerosis and distensibility of the aortic wall in vivo and is usually used for the atherosclerosis research[2].
Nitidine chloride, a potential anti-malarial lead compound derived from Zanthoxylum nitidum (Roxb) DC, exerts potent anticancer activity through diverse pathways, including inducing apoptosis, inhibiting STAT3 signaling cascade, DNA topoisomerase 1 and 2A, ERK and c-Src/FAK associated signaling pathway. Nitidine chloride inhibits LPS-induced inflammatory cytokines production via MAPK and NF-kB pathway[1][2][3][4][5][6].
JH-XIV-68-3 is a selective macrocyclic inhibitor of DYRK1A/B. JH-XIV-68-3 displays selectivity for DYRK1A and close family member DYRK1B in biochemical and cellular assays. JH-XIV-68-3 demonstrates antitumor efficacy in head and neck squamous cell carcinoma (HNSCC) cell lines[1].
Chromeceptin is an IGF signaling pathway inhibitor. Chromeceptin suppresses IGF2 at mRNA and protein levels in hepatocyte and HCC cells. Chromeceptin inhibits the Phosphorylation levels of AKT and mTOR[1].
UNC-CA359 is a potent epidermal growth factor receptor (EGFR) inhibitor, with an IC50 value of 18 nM. UNC-CA359 exhibits strong anti-tumor activity, can be used to Chordoma research[1].
CSF1R-IN-8 (Compound 22) is a CSF-1R inhibitor with an IC50 of 0.012 μM[1].
Pentagamavunon-1 (PGV-1), a Curcumin analog with oral activity, targets on several molecular mechanisms to induce apoptosis including inhibition of angiogenic factors cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF). PGV-1 inhibits NF-κB activation[1].
Lapatinib-d5 is deuterium labeled Lapatinib. Lapatinib (GW572016) is a potent inhibitor of the ErbB-2 and EGFR tyrosine kinase domains with IC50 values against purified EGFR and ErbB-2 of 10.2 and 9.8 nM, respectively[1].
GNF-2 is a highly selective non-ATP competitive inhibitor of oncogenic Bcr-Abl activity (IC50 = 0.14 μM).IC50 value: 0.14 uM [1]Target: Bcr-Ablin vitro: Ba/F3 cells harboring native or T315I mutated Bcr-Abl constructs were treated with GNF-2 and AKIs. We monitored the effect of GNF-2 with AKIs on the proliferation and clonigenicity of the different Ba/F3 cells. In addition, we monitored the auto-phosphorylation activity of Bcr-Abl and JAK2 in cells treated with GNF-2 and AKIs [2]. GNF-2 increased the effects of AKIs on unmutated BCR/ABL. Interestingly, the combination of Dasatinib and GNF-2 overcame resistance of BCR/ABL-T315I in all models used in a synergistic manner [3].GNF-2 dose-dependently inhibited the proliferation of osteoclast precursors through the suppression of the M-CSFR c-Fms. In addition, GNF-2 accelerated osteoclast apoptosis by inducing caspase-3 and Bim expression. Furthermore, GNF-2 interfered with actin cytoskeletal organization and subsequently blocked the bone-resorbing activity of mature osteoclasts [4].in vivo: Combining PDMP and GNF-2 eliminated transplanted-CML-T315I-mutants in vivo and dose dependently sensitized primary cells from CML T315I patients to GNF-2-induced proliferation inhibition and apoptosis[5].
NVP-TAE 684 is a highly potent and selective ALK inhibitor, which blocks the growth of ALCL-derived and ALK-dependent cell lines with IC50 values between 2 and 10 nM.