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301836-41-9 (SB-431542)

1

Identification

SB-431542 SB-431542
Name SB-431542
Formula C22H16N4O3
MW 384.39
CAS No. 301836-41-9
EINECS
Smiles O=C(C1=CC=C(C=C1)C2=NC(C3=CC=C4OCOC4=C3)=C(N2)C5=NC=CC=C5)N
Synonyms SB 431542; SB431542; 4-(4-(benzo[d][1,3]dioxol-5-yl)-5-(pyridin-2-yl)-1H-imidazol-2-yl)benzamide
InChI InChI=1S/C22H16N4O3/c23-21(27)13-4-6-14(7-5-13)22-25-19(20(26-22)16-3-1-2-10-24-16)15-8-9-17-18(11-15)29-12-28-17/h1-11H,12H2,(H2,23,27)(H,25,26)
2

Introduction

SB-431542 is potent and selective inhibitor of the transforming growth factor-β (TGF-β) type I receptor activin receptor-like kinase ALK5 (IC50 = 94 nM) and its relatives ALK4 and ALK7.

Background Information

Inhibitor of the TGF-beta type I receptor kinase activity ......by AOBIOUS INC
<p>SB431542 is a selective ATP-competitive inhibitor of ALK5 (activin receptor-like kinase 5) with an IC50 value of 94 nM [1].</p><p>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].</p><p class="references">References:<br>[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.<br>[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.<br></p> ......by Apexbio Technology LLC
SB-431542 is potent and selective inhibitor of the transforming growth factor-β (TGF-β) type I receptor activin receptor-like kinase ALK5 (IC50 = 94 nM) and its relatives ALK4 and ALK7. IC50 value: 94 nM [1] Target: TGF-βReceptor in vitro: SB 431542 inhibits the activin type I receptor ALK4 and the nodal type I receptor ALK7, which are responsible for the phosphorylation of Smad2. SB 431542 has little effect on ALK1, ALK2, ALK3, and ALK6, which show phosphorylation of Smad1. SB 431542 is a selective inhibitor of endogenous activin but has no apparent effect on BMP signaling. SB 431542 could induce both Smad2/Smad4- and Smad3/Smad4-dependent transcription [2]. In A498 cells, SB 431542 inhibits both TGF-β1-induced collagen Iα1 and PAI-1 mRNA with IC50 of 60 nM and 50 nM, respectively. In addition, SB 431542 inhibits production of TGF-β1-induced fibronectin mRNA and protein with IC50 of 62 nM and 22 nM, respectively [3]. SB 431542 significantly suppresses TGF-β-induced G1 arrest, leading to accumulation of cells in the S phase of the cell cycle in FET, RIE, and Mv1Lu cells. SB 431542 also inhibits TGF-β-induced epithelial to mesenchymal transition (EMT) in NMuMG and PANC-1 cells [4]. SB 431542 blocks the TGF-β-mediated growth factors, including PDGF-A, FGF-2 and HB-EGF, leading to an increase in proliferation of MG63 cells. SB 431542 also inhibits TGF-β-induced c-Myc and p21 WAF1/CIP1 [6]. in vivo: SB 431542 triggers cytotoxic T lymphocyte (CTL) activities in the colon-26 carcinoma models and is most likely to produce antitumor immunological outcomes through alteration of DC function suppressed by TGF-β [5]. Protocol(Only for Reference) Cell Assay [6]: Cell line: MG63 and NIH3T3 Concentration: 0.3 uM Method: To explore the effects of ligands, MG63 and NIH3T3 cells are seeded at a density of 8 × 10 4 cells/well in 6-well plates and starved (0.1% FCS for MG63 cells and 0.5% FCS for NIH3T3 cells) for 24 hours before ligand stimulation. Media containing various ligands are exchanged at 48-hours intervals. Cells are trypsinized and counted by a Coulter counter on days 2, 4, and 6 after ligand stimulation. To explore the effects of constitutively active receptors, cells are seeded at a density of 2 × 105 cells/well in 6-well plates. The next day, cells are infected with adenoviruses carrying various cDNAs at a multiplicity of infection of 100. Cells are trypsinized and counted on day 3. Cell proliferation assay is performed in the presence of 0.3 μM SB 431542. Animal Model Study [5]: Animal Model: BALB/c mice receive intraperitoneal (i.p.) injections of colon-26 tumor cells. Formulation: DMSO Dosage: 1 μM solution, 100 μL/mouse Administration: Injected into peritoneal cavity Solubility: 1% DMSO/30% polyethylene glycol/1% Tween 80, , 30 mg/mL ......by MedChemexpress Co., Ltd.
SB-431542 is a novel small molecule inhibitor of the type I TGF-beta receptor, on a panel of human malignant glioma cell lines. SB-431542 blocked the phosphorylation and nuclear translocation of the SMADs, intracellular mediators of TGF-beta signaling, with decreased TGF-beta-mediated transcription. Furthermore, SB-431542 inhibited the expression of two critical effectors of TGF-beta-vascular endothelial growth factor and plasminogen activator inhibitor-1. SB-431542 treatment of glioma cultures inhibited proliferation, TGF-beta-mediated morphologic changes, and cellular motility. Together, our results suggest that small molecule inhibitors of TGF-beta receptors may offer a novel therapy for malignant gliomas by reducing cell proliferation, angiogenesis, and motility. (source: Mol Cancer Ther. 2004 Jun;3(6):737-45.) Shelf life: >2 years if stored properly Drug formulation: This drug may be formulated in DMSO ......by MedKoo Biosciences, Inc.
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. ......by Selleck Chemicals LLC
SB431542 is a potent and selective inhibitor of ALK5 with IC50 of 94 nM in a cell-free assay, 100-fold more selective for ALK5 than p38 MAPK and other kinases. ......by Target Molecule Corp.
3

Protocol(Only for Reference)

Cell Experiment

Cell lines D54MG, U87MG and U373MG cells
Conditions 10 μM, 24 hours
Method 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.
Source Apexbio Technology LLC

Animal Experiment

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.
Source Apexbio Technology LLC
4

Physical and Chemical Properties

Appearance:White to off-white solid EBNumber:EB000029031

Storage condition

Store at RT by Apexbio Technology LLC
Storage condition:Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years). Stock solution storage:0 - 4 C for short term (days to weeks), or -20 C for long term (months). Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs. by MedKoo Biosciences, Inc.

Solubility

Soluble in DMSO > 10 mM by Apexbio Technology LLC
DMSO ≥75mg/mL Water <1.2mg/mL Ethanol ≥42mg/mL by MedChemexpress Co., Ltd.
Soluble in DMSO, not in water by MedKoo Biosciences, Inc.
DMSO 77 mg/mL (200 mM) ; Water <1 mg/mL (<1 mM) ; Ethanol 3 mg/mL (7 mM) by Selleck Chemicals LLC
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Mechanism and Indication

Signaling Pathways TGF-beta/Smad
Target TGF-β Receptor
Research Area Cancer
Indications
6

Clinical Information

Product Name Sponsor & Collaborators Indications Start Date End Date Phase
SB-431542 - Not Found
SB-431542 - No Development Reported
7

Safety Data of SB-431542

Safety Statements : S22;S24/25
8

Spectral Information

9

Suppliers List

Company Price and Availability Country/Region
AOBIOUS INC 1mg/USD17() USA
Apexbio Technology LLC USA
CHEMSCENE, LLC 10mg/USD80(In stock);50mg/USD300(In stock);100mg/USD560(In stock) USA
Chemfuture Pharma Tech (Jiangsu) Ltd. China
MedChemexpress Co., Ltd. 10mg/USD80(In stock);50mg/USD300(In stock);100mg/USD560(In stock) USA
MedKoo Biosciences, Inc. USA
Pure Chemistry Scientific Inc. 10mg/USD65(In stock) USA
Selleck Chemicals LLC 10mg/USD110(In stock);10mM/1mLIn DMSO/USD143(In stock);50mg/USD470(In stock);200mg/USD1270(In stock) USA
Shanghai Haoyuan Chemexpress Co., Ltd. 10mg/USD86(In stock);50mg/USD338(In stock);100mg/USD630(In stock) China
Target Molecule Corp. 10mg/USD80();50mg/USD266();100mg/USD475() USA
10

Related Products

Other Forms of 301836-41-9

Name CAS No Formula MW

Recommended Compounds in TGF-β Receptor

Name CAS No Formula MW
K 02288 1431985-92-0 C20H20N2O4 352.38
ML347 1062368-49-3 C22H16N4O 352.39
DMH-1 1206711-16-1 C24H20N4O 380.44
LDN-212854 1432597-26-6 C25H22N6 406.48
SB-505124 (hydrochloride) 356559-13-2 C20H22ClN3O2 371.86
A 77-01 607737-87-1 C18H14N4 286.33
SB-505124 694433-59-5 C20H21N3O2 335.4
LY-364947 396129-53-6 C17H12N4 272.3
LDN193189 (Hydrochloride) 1062368-62-0 C25H26Cl4N6 552.33
SD-208 627536-09-8 C17H10ClFN6 352.75
RepSox 446859-33-2 C17H13N5 287.32
LDN193189 1062368-24-4 C25H22N6 406.48
A 83-01 909910-43-6 C25H19N5S 421.52
LY2109761 700874-71-1 C26H27N5O2 441.52
LY2157299 700874-72-2 C22H19N5O 369.42
GW788388 452342-67-5 C25H23N5O2 425.48
SB 525334 356559-20-1 C21H21N5 343.42
EW-7197 1352608-82-2 C22H18FN7 399.42
R-268712 879487-87-3 C20H18FN5O 363.39
ITD-1 1099644-42-4 C27H29NO3 415.52

Recommended Compounds in Same Indication

Name CAS No Formula MW
11

Route of Synthesis

12

References

[1]. Callahan JF, et al. Identification of novel inhibitors of the transforming growth factor beta1 (TGF-beta1) type 1 receptor (ALK5). J Med Chem, 2002, 45(5), 999-1001.

[2]. Inman GJ, et al. SB-431542 is a potent and specific inhibitor of transforming growth factor-beta superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7. Mol Pharmacol, 2002, 62(1), 65-74.

[3]. Laping NJ, et al. Inhibition of transforming growth factor (TGF)-beta1-induced extracellular matrix with a novel inhibitor of the TGF-beta type I receptor kinase activity: SB-431542. Mol Pharmacol, 2002, 62(1), 58-64.

[4]. Halder SK, et al. A specific inhibitor of TGF-beta receptor kinase, SB-431542, as a potent antitumor agent for human cancers. Neoplasia, 2005, 7(5), 509-521.

[5]. Tanaka H, et al. Transforming growth factor β signaling inhibitor, SB-431542, induces maturation of dendritic cells and enhances anti-tumor activity. Oncol Rep, 2010, 24(6), 1637-1643.

[6]. Matsuyama S, et al. SB-431542 and Gleevec inhibit transforming growth factor-beta-induced proliferation of human osteosarcoma cells. Cancer Res, 2003, 63(22), 7791-7798.

Protocol Reference

[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.

......by Apexbio Technology LLC
13

More Information

SB-431542

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