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Vismodegib

Product Name
Vismodegib
CAS No.
879085-55-9
Chemical Name
Vismodegib
Synonyms
Vismodegib;GDC-0449;Erivedge;101098;CS-1913;RG 3616;Vimodji;VisModegib Base;Vismodegib 13C7;Vismodegib, >=99%
CBNumber
CB52500590
Molecular Formula
C19H14Cl2N2O3S
Formula Weight
421.3
MOL File
879085-55-9.mol
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Vismodegib Property

Melting point:
179-181°C
Boiling point:
561.6±50.0 °C(Predicted)
Density 
1.440
storage temp. 
-20°
solubility 
Soluble in DMSO (up to 200 mg/ml) or in Ethanol (up to 10 mg/ml with warming)
form 
White solid.
pka
10.72±0.70(Predicted)
color 
Off-white or beige
Stability:
Stable for 2 years from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 3 months.
InChI
InChI=1S/C19H14Cl2N2O3S/c1-27(25,26)13-6-7-14(17(21)11-13)19(24)23-12-5-8-16(20)15(10-12)18-4-2-3-9-22-18/h2-11H,1H3,(H,23,24)
InChIKey
BPQMGSKTAYIVFO-UHFFFAOYSA-N
SMILES
C(NC1=CC=C(Cl)C(C2=NC=CC=C2)=C1)(=O)C1=CC=C(S(C)(=O)=O)C=C1Cl
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Safety

HS Code 
29333990
Hazardous Substances Data
879085-55-9(Hazardous Substances Data)
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Hazard and Precautionary Statements (GHS)

Symbol(GHS)
Signal word
Danger
Hazard statements

H360May damage fertility or the unborn child

H373May cause damage to organs through prolonged or repeated exposure

H400Very toxic to aquatic life

H410Very toxic to aquatic life with long lasting effects

Precautionary statements

P260Do not breathe dust/fume/gas/mist/vapours/spray.

P273Avoid release to the environment.

P314Get medical advice/attention if you feel unwell.

P391Collect spillage. Hazardous to the aquatic environment

P501Dispose of contents/container to..…

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N-Bromosuccinimide Price

Cayman Chemical
Product number
13613
Product name
GDC-0449
Purity
≥98%
Packaging
5mg
Price
$75
Updated
2021/12/16
Cayman Chemical
Product number
13613
Product name
GDC-0449
Purity
≥98%
Packaging
10mg
Price
$135
Updated
2021/12/16
Cayman Chemical
Product number
13613
Product name
GDC-0449
Purity
≥98%
Packaging
50mg
Price
$338
Updated
2021/12/16
Cayman Chemical
Product number
13613
Product name
GDC-0449
Purity
≥98%
Packaging
25mg
Price
$244
Updated
2021/12/16
TRC
Product number
V674700
Product name
Vismodegib
Packaging
50mg
Price
$375
Updated
2021/12/16
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Vismodegib Chemical Properties,Usage,Production

Description

In January 2012, the US FDA approved vismodegib (also referred to as GDC-0449) for the treatment of adults with metastatic basal cell carcinoma (BCC), with locally advanced BCC that has recurred following surgery or who are not candidates for surgery or radiation. Vismodegib inhibits the Hh sig?naling pathway by functioning as an antagonist of SMO thereby inhibiting the activation of Hedgehog target genes, resulting in decreased downstream pro?duction of proliferation factors. The IC50 of vismodegib in a Hedgehog?responsive cell line derived from human embryonic palatal mesenchyme cells was 2.8 nM. In preclinical in vivostudies, vismodegib at 12.5 mg/kg (bid) caused complete regression of tumors in a Hh pathway dependent medulloblas?tomaallograft model generated from Ptch+/-mice. A synthesis of vismodegib starting from 2-chloro-5-nitro aniline and employing a Negishi coupling with 2-pyridyl zinc iodide as a key step has been reported.

Chemical Properties

White Solid

Originator

Curis/Genentech (United States)

Uses

Vismodegib targets the Hedgehog (Hh) pathway. Inhibition of the Hh signaling may be effective in the treatment and prevention of many types of human cancers. Potent Hedgehog inhibitor.

Uses

Vismodegib (GDC-0449) is a potent, novel and specific hedgehog inhibitor with IC50 of 3 nM and also inhibits P-gp with IC50 of 3.0 μM.

Definition

ChEBI: A benzamide obtained by formal condensation between the carboxy group of 2-chloro-4-(methylsulfonyl)benzoic acid and the anilino group of 4-chloro-3-(pyridin-2-yl)aniline. Used for the treatment metastatic basal cell carcinoma.

brand name

Erivedge

Clinical Use

Antineoplastic agent:
Treatment of basal cell carcinoma which is inappropriate for surgery or radiotherapy

Synthesis

The synthesis began with selective iodination of commercial carboxylic acid 179, affording trisubstituted arene 180 in 73% yield. A Curtius reaction then converted 180 to carbamate 181 in 84% 52 yield, and this was followed by a palladium(0)-catalyzed borylation of 181 which furnished Suzuki coupling partner 182 in 91% yield. Pinacol borane 182 was exposed to commercial 2-bromopyridine under conventional cross-coupling conditions to furnish biaryl 183, which underwent Boc-deprotection in quantitative conversion to generate 184. Amide bond formation with acid chloride 185 (readily available from the corresponding commercial acid) produced vismodegib (XXVIII) in 99% yield.

target

Hedgehog

Drug interactions

Potentially hazardous interactions with other drugs
Antibacterials: concentration possibly reduced by rifampicin - avoid.
Antidepressants: concentration possibly reduced by St John’s wort - avoid.
Antiepileptics: concentration possibly reduced by carbamazepine, fosphenytoin and phenytoin - avoid.
Antipsychotics: avoid with clozapine, increased risk of agranulocytosis.

Metabolism

Vismodegib is hepatically metabolised by CYP2C9 and CYP3A4, however more than 98
% of total systemic vismodegib is not metabolised. Metabolic pathways of vismodegib include oxidation, glucuronidation, and pyridine ring cleavage. The two most abundant oxidative metabolites recovered in faeces are produced in vitro by recombinant CYP2C9 and CYP3A4/5.
Vismodegib is slowly eliminated by a combination of metabolism and excretion of parent drug, the majority is recovered in the faeces (82
%). Vismodegib and its metabolites are eliminated mainly by the hepatic route.

storage

Store at -20°C

References

1) Rominger et al. (2009), Evidence for allosteric interactions of antagonist binding to the smoothened receptor; J. Pharmacol. Exp. Therap., 329 995 2) Tian et al. (2012), The hedgehog pathway inhibitor GDC-0449 alters intracellular Ca2+ homeostasis and inhibits cell growth in cisplatin-resistant lung cancer cells; Anticancer Res., 32 89 3) Zhang et al. (2009), Hedgehog pathway inhibitor HhAntag691 is a potent inhibitor of ABCG2/BCRP and ABCB1/Pgp; Neoplasia, 11 96 4) Cirrone and Harris (2012), Vismodegib anf the hedgehog pathway: a new treatment for basal cell carcinoma; Clin. Ther., 34 2039 5) Wu et al. (2017), Smoothened antagonist GDC-0449 (Vismodegib) inhibits proliferation and triggers apoptosis in colon cancer cell lines; Exp. Ther. Med., 13 2529 6)Singh et al. (2011) Hedgehog signaling antagonist GDC-0449 (Vismodegib) inhibits pancreatic cancer stem cell characteristics: molecular mechanisms; PLoS One 6?e27306 7) Rudin et al. (2009) Treatment of medulloblastoma with hedgehog pathway inhibitor GDC-0449; N. Engl. J. Med., 361?1173 8) Von Hoff et al. (2009) Inhibition of the hedgehog pathway in advanced basal-cell carcinoma; N. Engl. J. Med., 361?1164

Vismodegib Preparation Products And Raw materials

Raw materials

Preparation Products

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Vismodegib Suppliers

Beijing Jingzi Pharmaceutical Technology Co., Ltd.
Tel
15011485209
Email
17241816@qq.com
Country
China
ProdList
81
Advantage
58
Shanghai Zhixin Chemical Technology Co., Ltd.
Tel
021-60441077 18701958033
Fax
021-60441077
Email
shzxchem@163.com
Country
China
ProdList
590
Advantage
58
Wuhan Shanhai Zhihe Biotechnology Co., Ltd.
Tel
17771424646
Email
shoubull@126.com
Country
China
ProdList
967
Advantage
58
Olix (Shanghai) Pharmaceutical Technology Co., Ltd
Tel
17316404525
Email
209533805@qq.com
Country
China
ProdList
9787
Advantage
58
Elucigen bio
Tel
13501719342
Email
wayne.zheng@elucigenbio.com
Country
China
ProdList
4649
Advantage
58
Shanghai Boyle Chemical Co., Ltd.
Tel
Fax
86-21-57758967
Email
sales@boylechem.com
Country
China
ProdList
2922
Advantage
55
J & K SCIENTIFIC LTD.
Tel
010-82848833 400-666-7788
Fax
86-10-82849933
Email
jkinfo@jkchemical.com
Country
China
ProdList
94657
Advantage
76
Chembest Research Laboratories Limited
Tel
+86-21-20908456
Fax
021-58180499
Email
sales@BioChemBest.com
Country
China
ProdList
6005
Advantage
61
Capot Chemical Co., Ltd
Tel
+86 (0) 571 85 58 67 18
Fax
0086-571-85864795
Email
sales@capotchem.com
Country
China
ProdList
18207
Advantage
66
JinYan Chemicals(ShangHai) Co.,Ltd.
Tel
13817811078
Fax
86-021-50426522,50426273
Email
sales@jingyan-chemical.com
Country
China
ProdList
9976
Advantage
60
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View Lastest Price from Vismodegib manufacturers

BEIJING SJAR TECHNOLOGY DEVELOPMENT CO., LTD.
Product
Vismodegib 879085-55-9
Price
US $0.00/g
Min. Order
1g
Purity
More Than 99%
Supply Ability
100kg/Month
Release date
2024-07-24
Senova Technology Co. Ltd.
Product
vismodegib 879085-55-9
Price
US $0.00-0.00/g
Min. Order
1g
Purity
98%
Supply Ability
10KG
Release date
2023-12-14
Qiuxian Baitai New Material Co., LTD
Product
GDC-0449 879085-55-9
Price
US $73.00/mg
Min. Order
1KG
Purity
98%
Supply Ability
50ton/Month
Release date
2021-12-21

879085-55-9, VismodegibRelated Search:


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  • Inhibitor
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