Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C22H16N4O3 |
| Molecular Weight | 384.3874 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
NC(=O)C1=CC=C(C=C1)C2=NC(=C(N2)C3=CC=CC=N3)C4=CC5=C(OCO5)C=C4
InChI
InChIKey=FHYUGAJXYORMHI-UHFFFAOYSA-N
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)
| Molecular Formula | C22H16N4O3 |
| Molecular Weight | 384.3874 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
SB-431542 was identified as a TGF-beta receptor type-1 inhibitor (IC50 = 94 nM) by scientists at GlaxoSmithKline. It has subsequently been studied in animal and cell models as a potential cancer treatment, although these efforts have been discontinued. Of note, SB-431542 was also used in a wound healing study where it was found to abolish the improved healing normally enhanced by treatment with Povidone-iodine.
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: P36897 Gene ID: 7046.0 Gene Symbol: TGFBR1 Target Organism: Homo sapiens (Human) |
94.0 nM [IC50] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Secondary | Unknown Approved UseUnknown |
|||
| Primary | Unknown Approved UseUnknown |
PubMed
| Title | Date | PubMed |
|---|---|---|
| TGF-beta1/Smad7 signaling stimulates renal tubulointerstitial fibrosis induced by AAI. | 2008 |
|
| Transforming growth factor beta2 regulates growth and differentiation of pulp cells via ALK5/Smad2/3. | 2008 Apr |
|
| Transforming growth factor-beta1 regulates the fate of cultured spinal cord-derived neural progenitor cells. | 2008 Apr |
|
| Transforming growth factor-beta stimulates intestinal epithelial focal adhesion kinase synthesis via Smad- and p38-dependent mechanisms. | 2008 Aug |
|
| FK506 can activate transforming growth factor-beta signalling in vascular smooth muscle cells and promote proliferation. | 2008 Aug 1 |
|
| TGF-beta inhibits prolactin-induced expression of beta-casein by a Smad3-dependent mechanism. | 2008 Aug 1 |
|
| NANOG is a direct target of TGFbeta/activin-mediated SMAD signaling in human ESCs. | 2008 Aug 7 |
|
| TGFbeta and SMADs talk to NANOG in human embryonic stem cells. | 2008 Aug 7 |
|
| Gamma-irradiation enhances RECK protein levels in Panc-1 pancreatic cancer cells. | 2008 Feb 29 |
|
| Improvement of the breaking strength of wound by combined treatment with recombinant human G-CSF, recombinant human M-CSF, and a TGF-beta1 receptor kinase inhibitor in rat skin. | 2008 May |
|
| Expression of the type III TGF-beta receptor is negatively regulated by TGF-beta. | 2008 May |
|
| Neurokinin-A inhibits cell cycle activators in K562 cells and activates Smad 4 through a non-canonical pathway: a novel method in neural-hematopoietic axis. | 2008 Nov 15 |
|
| Constitutive Smad signaling and Smad-dependent collagen gene expression in mouse embryonic fibroblasts lacking peroxisome proliferator-activated receptor-gamma. | 2008 Sep 19 |
|
| TGF-beta inhibits CYP17 transcription in H295R cells acting via activin receptor-like kinase 5. | 2009 |
|
| Graded Smad2/3 activation is converted directly into levels of target gene expression in embryonic stem cells. | 2009 |
|
| Overexpression of manganese superoxide dismutase in human dermal fibroblasts enhances the contraction of free floating collagen lattice: implications for ageing and hyperplastic scar formation. | 2009 Apr |
|
| The core-aldehyde 9-oxononanoyl cholesterol increases the level of transforming growth factor beta1-specific receptors on promonocytic U937 cell membranes. | 2009 Apr |
|
| SB-431542 inhibition of scar formation after filtration surgery and its potential mechanism. | 2009 Apr |
|
| p38-Mitogen-activated protein kinase stimulated steroidogenesis in granulosa cell-oocyte cocultures: role of bone morphogenetic proteins 2 and 4. | 2009 Apr |
|
| Dual functions for LTBP in lung development: LTBP-4 independently modulates elastogenesis and TGF-beta activity. | 2009 Apr |
|
| Synthesis and biological evaluation of 1,2,4-trisubstituted imidazoles and 1,3,5-trisubstituted pyrazoles as inhibitors of transforming growth factor beta type 1 receptor (ALK5). | 2009 Aug 15 |
|
| Gap junction reduction in cardiomyocytes following transforming growth factor-beta treatment and Trypanosoma cruzi infection. | 2009 Dec |
|
| Differential effects of TGFbeta and vitreous on the transformation of retinal pigment epithelial cells. | 2009 Dec |
|
| Reduction of beta-amyloid-induced neurotoxicity on hippocampal cell cultures by moderate acidosis is mediated by transforming growth factor beta. | 2009 Feb 18 |
|
| TGF-beta-mediated activation of RhoA signalling is required for efficient (V12)HaRas and (V600E)BRAF transformation. | 2009 Feb 19 |
|
| TGFbeta-stimulated Smad1/5 phosphorylation requires the ALK5 L45 loop and mediates the pro-migratory TGFbeta switch. | 2009 Jan 21 |
|
| Transcriptome profiling reveals TGF-beta signaling involvement in epileptogenesis. | 2009 Jul 15 |
|
| Mesendodermal signals required for otic induction: Bmp-antagonists cooperate with Fgf and can facilitate formation of ectopic otic tissue. | 2009 Jun |
|
| Myostatin reduces Akt/TORC1/p70S6K signaling, inhibiting myoblast differentiation and myotube size. | 2009 Jun |
|
| Disruption of bidirectional oocyte-cumulus paracrine signaling during in vitro maturation reduces subsequent mouse oocyte developmental competence. | 2009 May |
|
| Tumour-derived prostaglandin E and transforming growth factor-beta synergize to inhibit plasmacytoid dendritic cell-derived interferon-alpha. | 2009 Nov |
|
| A chemical platform for improved induction of human iPSCs. | 2009 Nov |
|
| Signaling pathways controlling pluripotency and early cell fate decisions of human induced pluripotent stem cells. | 2009 Nov |
|
| Autocrine TGF-beta signaling maintains tumorigenicity of glioma-initiating cells through Sry-related HMG-box factors. | 2009 Nov 6 |
|
| A small-molecule inhibitor of tgf-Beta signaling replaces sox2 in reprogramming by inducing nanog. | 2009 Nov 6 |
|
| Nodal signaling via an autocrine pathway promotes proliferation of mouse spermatogonial stem/progenitor cells through Smad2/3 and Oct-4 activation. | 2009 Oct |
|
| Activin/Nodal inhibition alone accelerates highly efficient neural conversion from human embryonic stem cells and imposes a caudal positional identity. | 2009 Oct 6 |
|
| Diabetes-relevant regulation of cultured blood outgrowth endothelial cells. | 2009 Sep |
|
| Platelet-derived growth factor and transforming growth factor-beta modulate the expression of matrix metalloproteinases and migratory function of human airway smooth muscle cells. | 2009 Sep |
|
| Extra-ovarian expression and activity of growth differentiation factor 9. | 2009 Sep |
|
| Desmoid cell motility is induced in vitro by rhEGF. | 2009 Sep |
|
| In vitro differentiation of retinal cells from human pluripotent stem cells by small-molecule induction. | 2009 Sep 1 |
|
| VEGF and inhibitors of TGFbeta type-I receptor kinase synergistically promote blood-vessel formation by inducing alpha5-integrin expression. | 2009 Sep 15 |
|
| Biphasic effects of selective inhibition of transforming growth factor beta1 activin receptor-like kinase on LPS-induced lung injury. | 2010 Feb |
|
| Fuzheng Huayu recipe and vitamin E reverse renal interstitial fibrosis through counteracting TGF-beta1-induced epithelial-to-mesenchymal transition. | 2010 Feb 17 |
|
| BMP-3 promotes mesenchymal stem cell proliferation through the TGF-beta/activin signaling pathway. | 2010 Jun |
|
| Inhibition of transforming growth factor-beta signalling attenuates interleukin (IL)-18 plus IL-2-induced interstitial lung disease in mice. | 2010 Jun |
|
| MicroRNA-224 is involved in transforming growth factor-beta-mediated mouse granulosa cell proliferation and granulosa cell function by targeting Smad4. | 2010 Mar |
|
| Interleukin 11 and activin A synergise to regulate progesterone-induced but not cAMP-induced decidualization. | 2010 Mar |
|
| Transcriptional regulation of the small GTPase RhoB gene by TGF{beta}-induced signaling pathways. | 2010 Mar |
Sample Use Guides
100 random samples were collected from breast cancer patients who had undergone surgical resection. Mice were injected with cell suspensions containing MDA-MB-231-shCon \ MDA-MB-231-shNodal \ MCF-7-Nodal \ MCF- 7-Con. Three days after inoculation mice were dosed with 10 mg/kg of SB-431542 via intraperitoneal injection for four weeks on alternating days. After 4 weeks treatment with SB-431542 demonstrated tumor growth rate inhibition and weekend tumorigenicity.
Route of Administration:
Intraperitoneal
Renal epithelial carcinoma A498 cells were serum starved for 24 h and then treated with various concentrations of SB-431542 for 48 hours to determine cellular toxicity. Cells survived with up tp 10 uM of SB-4831542 for 48 hours, indicating an LD50 > 30 uM. Furthermore, at a concentration of 1 uM SB-242235 was able to prevent the TGF-B–induced nuclear accumulation of Smad
proteins. A dose response curve using 0, 50, 250, 500, and 700 nM SB-431542 was established and an IC50 of 50 nM was reported for inhibition of TGF-B1–induced nuclear fluorescence.
| Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 08:19:53 GMT 2023
by
admin
on
Sat Dec 16 08:19:53 GMT 2023
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| Record UNII |
E1557V1V0N
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| Record Status |
Validated (UNII)
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| Record Version |
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E1557V1V0N
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DTXSID7042693
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4521392
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91108
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301836-41-9
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SB-431542
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admin on Sat Dec 16 08:19:53 GMT 2023 , Edited by admin on Sat Dec 16 08:19:53 GMT 2023
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