BAF3

Zongertinib is a human HER2-selective tyrosine kinase inhibitor, a novel TK that is highly selective for covalent binding to the HER2 tyrosine kinase domain (TKD).Zongertinib exhibits antitumor activity with inhibitory effects on pHER2 and EGF.

BI-2865 is a non-covalent pan-KRAS inhibitor.BI-2865 binds to KRAS WT, G12C, G12D, G12V, and G13D mutants with KD values of 6.9, 4.5, 32, 26, and 4.3 nM, respectively.BI-2865 showed antiproliferative activity in BaF3 cells expressing KRAS G12C, G12D, or G12V mutants[1] . BI-2865 showed antiproliferative activity on BaF3 cells expressing KRAS G12C, G12D or G12V mutants, with an average IC50 value of approximately 140 nM.[1]

BI-4020 is a fourth-generation, orally active, and non-covalent inhibitor of EGFR tyrosine kinase. It exhibits activity against the triple mutant EGFR del19 T790M C797S variant (IC50=0.2 nM in BaF3 cell lines), the double mutant EGFR del19 T790M and primary mutant EGFR del19 (IC50=1 nM), and EGFR wt (IC50=190 nM). BI-4020 also shows high kinome selectivity and good DMPK properties.

Nilotinib (AMN107) is a Bcr-Abl tyrosine kinase inhibitor with oral activity. Nilotinib has antitumor activity and may be used for the treatment of Imatinib-resistant chronic myelogenous leukemia (CML).

Eltrombopag (SB-497115-GR), an orally active thrombopoietin receptor agonist with megakaryopoiesis stimulating activity, binds to and stimulates the platelet thrombopoietin receptor (TPO-R or CD110).

Imatinib (STI571) is a multi-targeted receptor tyrosine kinase inhibitor that selectively inhibits the kinase activities of BCR ABL, v-Abl, PDGFR, and c-kit with oral activity. Imatinib has antitumor activity for the treatment of chronic granulocytic leukemia.

Eltrombopag Olamine (Eltrombopag diethanolamine salt) is an orally active small-molecule, nonpeptide thrombopoietin receptor agonist that stimulates megakaryopoiesis. It binds to and activates the transmembrane domain of the platelet thrombopoietin receptor (TPO-R or CD110), promoting the proliferation and differentiation of megakaryocytic cells and enhancing platelet production.

NVP-BVU972 is a selective and potent Met inhibitor with IC50 of 14 nM.

Homoharringtonine (HHT) is a natural alkaloid that inhibits the translation of proteins and is cytotoxic. Homoharringtonine acts on the ribosomes of tumor cells to inhibit the elongation step of protein translation, thereby inhibiting protein synthesis, and has antitumor activity.

SHP099 (SHP099 free base) free base is an effective, selective, orally bioavailable, and efficacious SHP2 inhibitor (IC50 =0.07 μM and p-ERK modulation in cells IC50 = 0.250 μM). SHP099 shows dose-dependent pathway inhibition and antitumor activity in xenograft models.

SCH-336 is a CB2 receptor agonist (Ki-1.8 nM, EC50-2 nM) with effective, selective, and oral activity. SCH-336 is also bioactive against CB1 receptor, and is 100 times more selective to CB2 receptor than CB1. SCH-336 reduced the binding of guanosine 5' -3-o -(sulfur) triphosphate to the membrane containing hCB, inhibited BaF3 CB2 cell migration, inhibited leukocyte migration in mouse delayed hypersensitivity models, and inhibited antigen-induced pulmonary eosinophilia in mouse allergy models.

c-Kit-IN-3 D-tartrate is a potent and selective c-KIT kinase inhibitor (IC50s: 4 nM, 8 nM for c-KIT wt, and c-KIT T670I).

c-Kit-IN-3 hydrochloride is a potent and selective c-KIT kinase inhibitor (IC50s: 4 nM, 8 nM for c-KIT wt, and c-KIT T670I).

c-Kit-IN-3 tartrate is a potent and selective c-KIT kinase inhibitor (IC50s: 4 nM, 8 nM for c-KIT wt, and c-KIT T670I).

JND4135, a type II TRK inhibitor, exhibits IC50 values targeting TRKA, TRKB, and TRKC at 2.79, 3.19, and 3.01 nM, respectively. It can overcome resistance due to TRKxDFG and other mutations in the BaF3 stable model, inhibiting the phosphorylation of TRKs WT, xDFG mutations, and their downstream signaling molecules. Additionally, JND4135 induces G0 G1 phase arrest and cell apoptosis (apoptosis) in BaF3–CD74-TRKA-G667C cells. This compound also demonstrates antitumor activity in a BaF3-CD74-TRKA-G667C mouse xenograft model by suppressing tumor growth.

FLT3 HDAC-IN-1 is a dual inhibitor targeting FLT3 and HDAC, with IC50 values of 30.4 nM for FLT3 and 52.4, 14.7 nM for HDAC1 3, respectively. It induces apoptosis in MV-4-11 cells and exhibits antiproliferative effects against BaF3 cells transformed by FLT3 mutations. FLT3 HDAC-IN-1 is useful for research on refractory solid tumors and hematological malignancies.

C-Kit-IN-8 (Compound 53) acts as an inhibitor of c-Kit kinase, hampering uKIT kinase activity with an IC50 greater than 1 μM. Additionally, it inhibits the proliferation of both wild-type and mutant GIST430 and BaF3 cancer cells, exhibiting an IC50 greater than 0.1 μM.

FLT3-IN-28 (Compound 12y) is an orally active FLT3 inhibitor with antitumor properties. It selectively targets cancer cells with FLT3 internal tandem duplication (ITD) mutations, demonstrating IC50 values of 85, 290, 130, 65, and 220 nM against BaF3-FLT3-ITD, BaF3-TEL-VEGFR2, MV4-11, MOLM-13, and MOLM-14 cell lines, respectively. These lines include acute myeloid leukemia (AML) cells harboring FLT3-ITD mutations such as MV4-11 and MOLM-13 14. The compound also reduces phosphorylation levels of FLT3 and STAT5 in MOLM-13 cells, leading to cell cycle arrest and apoptosis. With an oral bioavailability of 19.2% in SD rats, FLT3-IN-28 extends survival in a dose-dependent manner in MOLM-13 xenografted NSG mouse models. It holds promise for research in FLT3-ITD-related cancer studies.

CQ1373 is a potent RET inhibitor that demonstrates cellular activity against BaF3 cells expressing CCDC6-RET, CCDC6-RET-G810C, and CCDC6-RET-G810R, with IC50 values of 13.0, 25.7, and 28.4 nM, respectively. It shows excellent selectivity for wild-type RET and solvent front mutants G810C R, with IC50 values of 4.2, 7.1, and 32.4 nM. CQ1373 inhibits RET phosphorylation and downstream signaling through SHC. Additionally, it induces apoptosis (Apoptosis) and cell cycle arrest in BaF3 cells. CQ1373 possesses antitumor efficacy, making it a candidate for cancer research.

BW710 is an orally active inhibitor specifically targeting fibroblast growth factor receptor 2 (FGFR2). It effectively inhibits the proliferation of BaF3-FGFR2 cells with an IC50 value of 2.8 nM. BW710 completely suppresses FGFR2 enzymatic activity and demonstrates selectivity among 75 tyrosine kinases, including FGFR1, FGFR3, and FGFR4, at a 1 μM concentration. Additionally, BW710 impedes FGFR2 signaling and selectively inhibits the proliferation of cancer cells driven by FGFR2. It exhibits promising pharmacokinetic properties, with an oral bioavailability of 29% in mice.

RET-IN-29 (Compound 8W) is a selective RET kinase inhibitor. It demonstrates inhibitory effects on BaF3 cells with the CCDC6-RETV804M mutation, with an IC50 of 0.715 μM. RET-IN-29 shows potential for research in non-small cell lung cancer (NSCLC).

Acrizanib (LHA510) is a VEGFR-2 inhibitor with an IC50 of 17.4 nM for BaF3-VEGFR-2.

Axl-IN-8 (NO.1) is a potent AXL inhibitor (IC50 < 1 nM) and also inhibits c-MET (IC50: 1-10 nM).

EGFR-IN-50 is a potent EGFR inhibitor targeting L858R resistance mutations, acting on TEL-EGFR-L858R-BaF3 and TEL-EGFR-T790M-L858R-BaF3 with GI50 values of 8 nM and 6.03 μM, respectively. EGFR-IN-50 exhibits anti-proliferative effects on cancer cells. .