A8249-10mg | SB 431542 [301836-41-9] Clinisciences

SB431542 is a selective ATP-competitive inhibitor of ALK5 (activin receptor-like kinase 5) with an IC50 value of 94 nM [1].

SB431542 showed most potent efficacy among the series of hits screened out. It inhibited TGF-β1-induced mRNA formation in A498 cells with IC50 value of 50 nM. It also markedly reduced TGF-β-induced nuclear accumulation of Smad proteins with IC50 value of 40 nM. SB431542 was found to be a selective inhibitor for ALK4, ALK5 and ALK7, suppresses the phosphorylation of Smad2. It showed no significant inhibition of ALK1, ALK2, ALK6 and showed weak effect on ALK3 at concentration of 10 μM [1, 2].

References:
[1] Callahan J F, Burgess J L, Fornwald J A, et al. Identification of novel inhibitors of the transforming growth factor β1 (TGF-β1) type 1 receptor (ALK5). Journal of medicinal chemistry, 2002, 45(5): 999-1001.
[2] Inman G J, Nicolás F J, Callahan J F, et al. SB-431542 is a potent and specific inhibitor of transforming growth factor-β superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7. Molecular pharmacology, 2002, 62(1): 65-74.

1. Ju Wei, Yi Shan, et al. "Anp32e promotes renal interstitial fibrosis by upregulating the expression of fibrosis-related proteins." Int J Biol Sci. 2022 Sep 25;18(15):5897-5912. PMID: 36263179
2. Te Zhang, Wenjie Xia, et al. "Super-enhancer hijacking LINC01977 promotes malignancy of early-stage lung adenocarcinoma addicted to the canonical TGF-β/SMAD3 pathway." J Hematol Oncol. 2022 Aug 18;15(1):114. PMID: 35982471
3. NAN CAO, NIGALA AIKEREMU, et al. "Inhibition of KIR2. 1 decreases pulmonary artery smooth muscle cell proliferation and migration." Int J Mol Med. 2022 Sep;50(3):119. PMID: 35856410
4. Liexi Jia, Yumei Diao, et al. "Methodological study of directed differentiation of pluripotent stem cells into corneal endothelial cells." Ann Transl Med. 2022 Apr;10(8):482. PMID: 35571395
5. Matthew P Pappas, Ning Xie, et al. "Defining the Skeletal Myogenic Lineage in Human Pluripotent Stem Cell-Derived Teratomas." Cells. 2022 May 9;11(9):1589. PMID: 35563894
6. Jingjing Zhang, Jinxin Qiu, et al. "Neuropilin-1 mediates lung tissue-specific control of ILC2 function in type 2 immunity." Nat Immunol. 2022 Feb;23(2):237-250. PMID: 35075279
7. MENG PAN, MIAO LI, et al. "Knockdown of ALDH1A3 reduces breast cancer stem cell marker CD44 via the miR-7-TGFBR2-Smad3-CD44 regulatory axis." Exp Ther Med. 2021 Oct;22(4):1093. PMID: 34504547
8. Meng Wang, Lingchen Wang, et al. "Icariin attenuates renal fibrosis in chronic kidney disease by inhibiting interleukin-1β/transforming growth factor-β-mediated activation of renal fibroblasts." Phytother Res. 2021 Nov;35(11):6204-6215. PMID: 34426999
9. Xiaoya An, Guoliang Wang, et al. "Novel cell culture paradigm prolongs mouse corneal epithelial cell proliferative activity in vitro and in vivo." Front Cell Dev Biol. 2021 Jun 30;9:675998. PMID: 34277619
10. Haibing Zhan, Xingchang Sun, et al. "LncRNA MEG3 Involved in NiO NPs-Induced Pulmonary Fibrosis via Regulating TGF-β1-Mediated PI3K/AKT Pathway." Toxicol Sci. 2021 Jul 16;182(1):120-131. PMID: 33895847
11. Nan Cao, Xuechun Tang, et al. "Galectin-3 participates in PASMC migration and proliferation by interacting with TGF-β1." Life Sci. 2021 Jun 1;274:119347. PMID: 33716065
12. Haibing Zhan, Xuhong Chang, et al. "LncRNA MEG3 mediates nickel oxide nanoparticles-induced pulmonary fibrosis via suppressing TGF-β1 expression and epithelial-mesenchymal transition process." Environ Toxicol. 2021 Jun;36(6):1099-1110. PMID: 33547861
13. Kexin Ma, Cailong Li, et al. "LncRNA Gm16410 regulates PM2. 5-induced lung Endothelial-Mesenchymal Transition via the TGF-β1/Smad3/p-Smad3 pathway." Ecotoxicol Environ Saf. 2020 Dec 1;205:111327. PMID: 32961493
14. Wang S, Zhang M, et al. "microRNA-141 inhibits TGF-β1-induced epithelial-to-mesenchymal transition through inhibition of the TGF-β1/SMAD2 signalling pathway in endometriosis." Arch Gynecol Obstet. 2020;10.1007/s00404-019-05429-w. PMID: 31903498
15. Wu F, Wu D, et al. "Generation of hepato-biliary organoids from human induced pluripotent stem cells." J Hepatol. 2019 Jan 7. pii: S0168-8278(19)30002-9. PMID: 30630011
16. Bae JS, Jeon Y, et al. "Depletion of MOB1A/B causes intestinal epithelial degeneration by suppressing Wnt activity and activating BMP/TGF-β signaling." Cell Death Dis. 2018 Oct 22;9(11):1083. PMID: 30349003

Hide ↑↑

Physical Appearance	A solid
Storage	Store at RT
M.Wt	384.39
Cas No.	301836-41-9
Formula	C₂₂H₁₆N₄O₃
Solubility	insoluble in H2O; ≥10.06 mg/mL in EtOH with ultrasonic; ≥19.22 mg/mL in DMSO
Chemical Name	4-[4-(1,3-benzodioxol-5-yl)-5-pyridin-2-yl-1H-imidazol-2-yl]benzamide
SDF	Download SDF
Canonical SMILES	C1OC2=C(O1)C=C(C=C2)C3=C(NC(=N3)C4=CC=C(C=C4)C(=O)N)C5=CC=CC=N5
Shipping Condition	Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice.
General tips	We do not recommend long-term storage for the solution, please use it up soon.

Cell experiment: [1]
Cell lines	D54MG, U87MG and U373MG cells
Preparation method	The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.
Reaction Conditions	10 μM, 24 hours
Applications	SB-431542 at both 0.1 and 1μmol/L had a modest effect on DNA synthesis, but at 10 μmol/L, there was a consistent 60% to 70% reduction of thymidine incorporation for D54MG, U87MG, and U373MG cells. No evidence of apoptotic cell death on SB-431542 treatment was detected either by direct observation or on propidium iodide flow cytometric analysis. Thus, SB-431542 acts to inhibit the proliferation of the tested malignant glioma lines.
Animal experiment: [2]
Animal models	BALB/c mice injected with colon-26 cells
Dosage form	Intraperitoneal injection, 1 μM
Applications	Intraperitoneal injection of SB-431542 resulted in triggering CTL activities against colon-26 targets compared with vehicle alone. Moreover, the CTL activity against colon-26 cells was more potent when treated with SB combined a ligand for toll-like receptor 4, OK-432, compared with OK-432 alone. Thus, SB-431542 is likely to produce antitumor immunological outcomes through alteration of DC function suppressed by TGFß.
Other notes	Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
References: [1] Hjelmeland M D, Hjelmeland A B, Sathornsumetee S, et al. SB-431542, a small molecule transforming growth factor-β-receptor antagonist, inhibits human glioma cell line proliferation and motility. Molecular Cancer Therapeutics, 2004, 3(6): 737-745. [2] Tanaka H, Shinto O, Yashiro M, et al. Transforming growth factor b signaling inhibitor, SB-431542, induces maturation of dendritic cells and enhances anti-tumor activity. Oncology reports, 2010, 24: 1637-1643.

Description	SB431542 is a potent and selective inhibitor of ALK5 with IC50 of 94 nM, 100-fold more selective for ALK5 than p38 MAPK and other kinases.
Targets	ALK5
IC50	94 nM