FLT3/D835Y-IN-1 (compound 13a) is a orally active, potent and selective FLT3 and FLT3/D835Y inhibitor, with IC50 values of 0.26 nM and 0.18 nM, respectively. FLT3/D835Y-IN-1 also blocks tumor growth, has anticancer efficacy, and can be used to research for AML (acute myeloid leukemia)[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Proliferation Assay
Cell Line:
Ba/F3-FLT3-ITD, Ba/F3-FLT3-ITD/D835Y, and Ba/F3-FLT3-ITD-F691L cell lines, AML cells[1]
Concentration:
100 nM
Incubation Time:
3 h
Result:
Inhibited Ba/F3-FLT3-ITD, Ba/F3-FLT3-ITD/D835Y, Ba/F3-FLT3-ITD-F691L, MV4-11, MOLM14, and MOLM14-ITD/D835Y proliferation, with GI50 values of 0.59, 0.73, 5.54, 1.30, 6.20, and 4.58 nM, respectively.
Western Blot Analysis
Cell Line:
MOLM14-ITD/D835Y and MOLM14-ITD/F691L cells[1].
Concentration:
3, 10, and 30 nM
Incubation Time:
16 h
Result:
Significantly inhibited the FLT3, AKT, ERK, and STAT5 pathways at lower dosages.
体内研究 (In Vivo)
FLT3/D835Y-IN-1 (10 mg/kg, IP, daily, 6 days per week) significantly suppresses tumor growth and exhibits potent antitumor activity against MOLM14-ITD/D835Y cells[1]. FLT3/D835Y-IN-1 (10 mg/kg, IV or Orally, single) displays extremely low AUC and high clearance[1]. Pharmacokinetic Parameters of FLT3/D835Y-IN-1 in ICR mice[1].
Parameters
13a
AUClast (ng*h/mL)
1360 ± 110
CL (L/h/kg)
6.96 ± 0.66
Vss (L/kg)
14.8 ± 0.7
T1/2 (h)
1.5 ± 0.1
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
NOD/SCID mice (6 weeks, male, nine mice per group)[1]
Dosage:
10 mg/kg
Administration:
IP, daily, 6 days per week, from day 7 to day 29
Result:
Significantly suppressed tumor growth.
Animal Model:
ICR mice (7–8 weeks, male)[1]
Dosage:
10 mg/kg, dissolved in a solution (10% DMSO, 40% PEG400, and 50% PBS)
Administration:
IV or Orally, single (Pharmacokinetic Analysis)
Result:
Displayed extremely low AUC and high clearance.
分子量
403.43
Formula
C22H21N5O3
CAS 号
2648799-49-7
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Lee JH, Shin JE, Kim W, et al. Discovery of indirubin-3′-aminooxy-acetamide derivatives as potent and selective FLT3/D835Y mutant kinase inhibitors for acute myeloid leukemia. Eur J Med Chem. 2022 Apr 21;237:114356.
DY131 (GSK 9089) is a potent and selective ERRγ and ERRβ agonist. DY131displays inactive against ERRα, ERα and ERβ[1][2]. DY131 also inhibits Smo signaling[3].
IC50 & Target[2]
ERRγ
ERRβ
体外研究 (In Vitro)
DY131 (0.1-30 μM; 5 days) treatment suppresses cell proliferation and reduces BrdUrd-positive cells in both LNCaP-ERRγ and LNCaP cells in a dose-dependent manner, with higher suppression in LNCaP-ERRγ clone[1]. DY131inhibits Shh induced accumulation of Smo::EGFP with an IC50 of 0.8 μM. DY131 suppresses SAG (100 nM) induced accumulation of Smo::EGFP in the primary cilium and Gli transcription activity with an IC50 of ~2 μM[3]. DY131 dramatically decreases phosphorylated histone H3 (pH3) marked proliferation of CGNPs induced by Shh[3]. A selective ERRγ agonist, DY131, inhibits the growth of the ERα-positive endometrial cancer cells but promoted that of the ERα-negative cancer cells[4].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Proliferation Assay[1]
Cell Line:
LNCaP-ERRγ and LNCaP cells
Concentration:
0.1 μM, 1 μM, 10 μM, 30 μM
Incubation Time:
5 days
Result:
Suppressed cell proliferation and reduced BrdUrd-positive cells in both LNCaP-ERRγ and LNCaP cells in a dose-dependent manner.
体内研究 (In Vivo)
DY131 (5 μg/kg; subcutaneous injection; every second day; for 12 days) treatment increases P450 side-chain cleavage (P450scc), StAR and HMGCoA reductase (HMGCR) while decreases hormone sensitive lipase (HSL) expressions[5].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
Mature male mice (C57BL/6) (8-10 week-old; ~24.3 g)[5]
Dosage:
5 μg/kg
Administration:
Subcutaneous injection; every second day; for 12 days
Result:
Increased P450scc, StAR and HMGCR while decreased HSL expressions.
分子量
311.38
Formula
C18H21N3O2
CAS 号
95167-41-2
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Yu S, et al. ERRgamma suppresses cell proliferation and tumor growth of androgen-sensitive and androgen-insensitive prostate cancer cells and its implication as a therapeutic target for prostate cancer. Cancer Res. 2007;67(10):4904-14.
[2]. Donna D. Yu, Barry Marc Forman. Identification of an agonist ligand for estrogen-related receptors ERRβ/γ. Bioorganic & Medicinal Chemistry Letters. 2005,15(5): 1311-1313.
[3]. Wang Y, et al. Selective identification of hedgehog pathway antagonists by direct analysis of smoothened ciliary translocation . ACS Chem Biol. 2012,15;7(6):1040-8.
[4]. Yamamoto T, et al. Estrogen-related receptor-γ regulates estrogen receptor-α responsiveness in uterine endometrial cancer. Int J Gynecol Cancer. 2012;22(9):1509-16.
[5]. A Pacwa, et al. Interplay between estrogen-related receptors and steroidogenesis-controlling molecules in adrenals. In vivo and in vitro study. Acta Histochem. 2018 Jul;120(5):456-467.
![dY-V-G 编码 [86030-52-6]](http://www.fluoroprobe.com/wp-content/uploads/2022/10/20221013_63486b03483ca.png)
![dY-V-G 编码 [86030-52-6]](http://www.fluoroprobe.com/wp-content/uploads/2022/10/20221013_63486b039d44a.jpg)
