itd-1

ITD-1 is a potent and highly selective TGFβ pathway inhibitor.

(+)-ITD-1 is an inhibitor of TGF-β, effectively inhibiting TGF-β2 with an IC50 of 0.46 μM. It promotes the degradation of the TGF-β type II receptor (TGFBR2) and the differentiation of cardiomyocytes. Additionally, it suppresses the formation of the mesoderm during the early differentiation of mouse embryonic stem cells (mESCs).

PROTAC FLT-3 degrader 1 is a PROTAC FLT-3 degrader of internal tandem duplication (ITD) with an IC50 of 0.6 nM and exhibits anti-proliferative activity.

FLT3-ITD/D835Y-IN-1 (Compound 1) is an inhibitor of FLT3-ITD and BCR-ABL. It induces pro-apoptotic (apoptosis) effects by inhibiting the FLT3 and BCR-ABL pathways, along with potentially other targets. This compound is applicable in acute myeloid leukemia (AML) research.

AC-4-130 is a direct STAT5 SH2 domain inhibitor that can disrupt STAT5 activation, dimerization, nuclear translocation, and STAT5-dependent gene transcription, inducing cell cycle arrest and apoptosis in leukemia cells, and can be used for the study of acute myeloid leukemia (AML).

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).

Desmorpholinyl Quizartinib-PEG2-COOH is a compound featuring an FLT-3 ligand and a PEG-based PROTAC linker. It is employed in the synthesis of PROTAC FLT-3 degrader 1, which serves as a degrader for the FLT-3 internal tandem duplication (ITD) through PROTAC technology. The degrader exhibits an IC50 of 0.6 nM.

HDAC10-IN-2 (compound 10c) is a potent and highly selective HDAC10 inhibitor (IC50 = 20 nM) that regulates autophagy in aggressive FLT3-ITD positive acute myeloid leukemia cells [1].

HDAC10-IN-1 (compound 13b) is a potent and highly selective HDAC10 inhibitor (IC50 = 58 nM) that regulates autophagy in aggressive FLT3-ITD positive acute myeloid leukemia cells [1].

FLT3/ITD-IN-1 (Compound 1) is a highly potent inhibitor of FLT3 internal tandem duplications (FLT3-ITD) with IC50 values of 38.2 nM for FLT3 and 144.1 nM for FLT3-ITD, and shows exceptional antiproliferative activities against several acute myeloid leukemia cell lines [1].

HP1328 is a highly effective inhibitor of FLT3 receptor tyrosine kinase with a specific focus on FLT3/ITD mutation. It belongs to the benzoimidazole scaffold-based compound family. Significantly reducing the leukemia burden, HP1328 effectively extends the survival of mice afflicted with FLT3/ITD leukemia [1].

FLT3/TrKA-IN-1 is a potent dual kinase inhibitor that targets FLT3 (IC50: 43.8 nM), FLT3-ITD (IC50: 97.2 nM), FLT3-TKD (IC50: 92.5 nM), and TrKA (IC50: 23.6 nM). FLT3/TrKA-IN-1 shows potential for acute myeloid leukaemia (AML) studies.

PDGFRα/FLT3-ITD-IN-1 are potent inhibitors of PDGFRα/FLT3, and their IC50 values are greater than 0.036 and 0.003 μM, respectively. PDGFRα/FLT3-ITD-IN-1 exhibits investigational potential in acute myeloid leukemia or chronic eosinophilic leukemia.

FI-700 is a novel and potent FLT3 inhibitor with promising antileukemia activity. FI-700 showed a potent IC(50) value against FLT3 kinase at 20 nmol/L in an in vitro kinase assay. FI-700 showed selective growth inhibition against mutant FLT3-expressing leukemia cell lines and primary acute myeloid leukemia cells, whereas it did not affect the FLT3 ligand (FL)-driven growth of Wt-FLT3-expressing cells. Oral administration of FI-700 induced the regression of tumors in a s.c. tumor xenograft model and increased the survival of mice in an i.v. transplanted model. Furthermore, FI-700 treatment eradicated FLT3/ITD-expressing leukemia cells, both in the peripheral blood and in the bone marrow. (Source: Clin Cancer Res. 2007 Aug 1;13(15 Pt 1):4575-82.)

BPR1J-340 is a potent and selective FLT3 inhibitor with potential anticancer activity. BPR1J-340 was identified as a novel potent FLT3 inhibitor by biochemical kinase activity (IC50 approximately 25 nM) and cellular proliferation (GC50 approximately 5 nM) assays. BPR1J-340 inhibited the phosphorylation of FLT3 and STAT5 and triggered apoptosis in FLT3-ITD(+) AML cells. The pharmacokinetic parameters of BPR1J-340 in rats were determined. BPR1J-340 also demonstrated pronounced tumor growth inhibition and regression in FLT3-ITD(+) AML murine xenograft models. The combination treatment of the HDAC inhibitor vorinostat (SAHA) with BPR1J-340 synergistically induced apoptosis via Mcl-1 down-regulation in MOLM-13 AML cells, indicating that the combination of selective FLT3 kinase inhibitors and HDAC inhibitors could exhibit clinical benefit in AML therapy.

GTP-14564 is a novel tyrosine kinase inhibitor that also inhibits wt-FLT3 and ITD-FLT3. GTP-14564 inhibits the growth of interleukin-3-independent Ba/F1 expressing ITD-FLT3 at 3 μ m, whereas a 30-fold higher concentration of GTP-14564 is required to inhibit the FLT3 ligand-dependent growth (wt-FLT3) of Ba/F3 expressing wild-type FLT3. F3 expressing wild-type FLT3 (wt-FLT3).

PF15, a selective FLT3-ITD degrader, serves as a PROTAC (proteolysis targeting chimera) tethering ligands for FLT3 kinase and CRBN. It exhibits a degradation concentration 50 (DC50) of 76.7 nM and notably impedes the proliferation of FLT3-ITD-positive cells. PF15 also reduces phosphorylation levels of FLT3 and STAT5 and demonstrates efficacy in inhibiting tumor growth in mouse models, suggesting potential applications in leukemia research [1].

PROTAC FLT3/CDK9 degrader-1, a potent dual degrader of FLT3 and CDK9, effectively induces apoptosis and targets protein degradation of FLT3 and CDK9. This compound holds research potential for FLT3-ITD mutated AML [1].

PF15 TFA, a PROTAC targeting FLT3 kinase and CRBN, exhibits selective degradation of FLT3-ITD with a DC50 of 76.7 nM. The compound potently suppresses proliferation in FLT3-ITD-positive cells, reduces phosphorylation levels of FLT3 and STAT5, and demonstrates inhibition of tumor growth in murine leukemia models [1].

HDAC10-IN-2 hydrochloride (compound 10c) is a highly potent and selective HDAC10 inhibitor with an IC50 of 20 nM, influencing autophagy in aggressive FLT3-ITD positive acute myeloid leukemia cells [1].

Antiproliferative agent-30 (Compound 8g) exhibits broad-spectrum antiproliferative activity, with IC50 values of 0.054 nM, 0.008 nM, and 0.144 nM against HCT-116, K562, and MV-4-11 cancer cell lines, respectively. It inhibits tubulin assembly, FLT3, and Abl1 kinases and shows vascular-disrupting capabilities. Additionally, it displays an anticancer effect against acute myeloid leukemia (AML) with FLT3-ITD-TKD mutations [1].

FLT3-IN-21 (compound LC-3), a potent FLT3 inhibitor with an IC50 value of 8.4 nM, induces apoptosis, arrests the cell cycle in the G1 phase, and effectively inhibits the proliferation of FLT3-ITD-positive AML cells MV-4-11 with an IC50 of 5.3 nM. In murine models, a daily dose of 10 mg/kg FLT3-IN-21 markedly inhibited tumor growth in the MV-4-11 xenograft model, achieving a tumor growth inhibition (TGI) of 92.16% [1].

FLT3-IN-20 (compound 34f) is a potent FLT3 inhibitor with IC50 values of 1 nM for FLT3-D835Y and 4 nM for FLT3-ITD. It shows anti-proliferative effects on FLT3-ITD-positive AML cell lines, with IC50s of 7 nM in MV4-11, 9 nM in MOLM-13, and 4 nM in a MOLM-13 variant harboring the FLT3-ITD-D835Y mutation. FLT3-IN-20 is utilized in cancer research [1].

Pomalidomide-C5-Dovitinib (compound 2) is a PROTAC linking Pomalidomide and Dovitinib via a CRBN connector, exhibiting potent antiproliferative activity in FLT3-ITD+ acute myeloid leukemia (AML) cells. It promotes ubiquitin-proteasome-dependent degradation of FLT3-ITD and KIT proteins, thereby inhibiting their downstream signaling pathways and presenting research potential in FLT3-ITD+ AML [1].