CAS 130370-60-4|Batimastat
| Common Name | Batimastat | ||
|---|---|---|---|
| CAS Number | 130370-60-4 | Molecular Weight | 477.640 |
| Density | 1.3±0.1 g/cm3 | Boiling Point | / |
| Molecular Formula | C23H31N3O4S2 | Melting Point | 236-238° |
| MSDS | ChineseUSA | Flash Point | / |
Names
| Name | (2S,3R)-N-hydroxy-N'-[(2S)-1-(methylamino)-1-oxo-3-phenylpropan-2-yl]-3-(2-methylpropyl)-2-(thiophen-2-ylsulfanylmethyl)butanediamide |
|---|---|
| Synonym | More Synonyms |
Batimastat BiologicalActivity
| Description | Batimastat is a potent broad spectrum MMP inhibitor with IC50 of 3, 4, 4, 6, and 20 nM for MMP-1, MMP-2, MMP-9, MMP-7 and MMP-3, respectively. |
|---|---|
| Related Catalog | Signaling Pathways >>Metabolic Enzyme/Protease >>MMPResearch Areas >>Cancer |
| Target | IC50: 3 nM (MMP-1), 4 nM (MMP-2), 4 nM (MMP-9), 6 nM (MMP-7), 20 nM (MMP-3)[1] |
| In Vitro | Batimastat (BB-94) is a potent matrix metalloproteinase inhibitor, exhibits an unexpected mode of binding. Batimastat inhibits gelatinases A and B with IC50 values of 4 nM and 10 nM, respectively. The IC50 with the structurally similar collagenase Ht-d is 6 nM, which is comparable with values for MMP-1 (3 nM), MMP-8 (10 nM), and MMP-3 (20 nM)[2]. CD30 shedding from the cell line Karpas299 can effectively be blocked by the hydroxamic acidbased metalloproteinase inhibitor Batimastat (BB-94, IC50=230 nM)[3]. |
| In Vivo | Intraperitoneal administration of Batimastat (BB-94) effectively blocks growth of human ovarian carcinoma xenografts and murine melanoma metastasis and delays the growth of primary tumors in an orthotopic model of human breast cancer without cytotoxicity and without affecting mRNA levels[2]. Batimastat (BB-94) is a synthetic matrix metalloproteinase inhibitor that has shown antineoplastic and antiangiogenic activity in various tumor models. Treatment with Batimastat (60 mg/kg i.p. every other day, for a total of eight injections) concomitantly with Cisplatin (4 mg/kg i.v., every 7 days for a total of three injections) completely prevents growth and spread of both xenografts, and all animals are alive and healthy on day 200[4]. Kaplan-Meier analysis of survival (at 48 h) shows that animals treated with Batimastat (BB-94) have increased survival (95.2%) in comparison with controls (75%), and differences are almost statistically significant (p=0.064)[5]. Matrix density is analyzed in saline- or Batimastat (40 mg/kg)-pretreated animals 4 h after E2 administration, the time point at which collagen density is observed to be at its lowest after hormone treatment[6]. |
| Animal Admin | Mice[5] Six-weeks-old female BALB/c mice are used. Mice are treated i.p. with Batimastat (BB-94, 50 mg/kg) 1 h before and 24 h post-infection. Batimastat is suspended at 50 mg/mL in DMSO and stored frozen at -20°C. Prior to use, it is diluted 20-fold in phosphate buffered saline (PBS), and 500 μL are injected into animals. Control mice are injected with 500 μL of 5% DMSO in PBS. Animals are sacrificed 48 h after i.c. challenge. Rats[6] Female Sprague-Dawley rats are administered a single physiological dose of E2 (40 μg/kg in a 0.9% NaCl, 0.4% EtOH vehicle) by intraperitoneal (i.p.) injection at the indicated time intervals prior to tissue collection at necropsy. This in vivo dose level of E2 has been shown to induce changes in uterine wet weight, tissue architecture, and gene expression characteristic of estrogen receptor activation. For all other experiments, animals are i.p. administered a single 40 μg/kg bolus of E2 4 h prior to tissue harvest, while control animals receive vehicle only in all studies. Batimastat is administered i.p. at a dose level (40 mg/kg in a 1× PBS, 0.1% Tween-20 vehicle) shown to be effective at inhibiting MMPs in vivo 4 h prior to E2 or saline control. |
| References | [1]. Yin Z, et al. Increased MMPs expression and decreased contraction in the rat myometrium during pregnancy and in response to prolonged stretch and sex hormones. Am J Physiol Endocrinol Metab. 2012 Jul 1;303(1):E55-70. [2]. Botos I, et al. Batimastat, a potent matrix mealloproteinase inhibitor, exhibits an unexpected mode of binding. Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):2749-54. [3]. Hansen HP, et al. Inhibition of metalloproteinases enhances the internalization of anti-CD30 antibody Ki-3 and the cytotoxic activity of Ki-3 immunotoxin. Int J Cancer. 2002 Mar 10;98(2):210-5. [4]. Giavazzi R, et al. Batimastat, a synthetic inhibitor of matrix metalloproteinases, potentiates the antitumor activity of cisplatin in ovarian carcinoma xenografts. Clin Cancer Res. 1998 Apr;4(4):985-92. [5]. Ricci S, et al. Inhibition of matrix metalloproteinases attenuates brain damage in experimental meningococcal meningitis. BMC Infect Dis. 2014 Dec 31;14:726. [6]. Russo LA, et al. Regulated expression of matrix metalloproteinases, inflammatory mediators, and endometrial matrix remodeling by 17beta-estradiol in the immature rat uterus. Reprod Biol Endocrinol. 2009 Nov 4;7:124. |
Chemical & Physical Properties
| Density | 1.3±0.1 g/cm3 |
|---|---|
| Melting Point | 236-238° |
| Molecular Formula | C23H31N3O4S2 |
| Molecular Weight | 477.640 |
| Exact Mass | 477.175598 |
| PSA | 161.07000 |
| LogP | 3.53 |
| Appearance of Characters | white to tan |
| Index of Refraction | 1.605 |
| Storage condition | Store at -20°C |
| Water Solubility | DMSO: ≥15mg/mL |
Safety Information
| RIDADR | NONH for all modes of transport |
|---|---|
| HS Code | 29349990 |
Articles59
More Articles| The sorting protein PACS-2 promotes ErbB signalling by regulating recycling of the metalloproteinase ADAM17. Nat. Commun. 6 , 7518, (2015) The metalloproteinase ADAM17 activates ErbB signalling by releasing ligands from the cell surface, a key step underlying epithelial development, growth and tumour progression. However, mechanisms acut... | |
| Inside-out Regulation of Ectodomain Cleavage of Cluster-of-Differentiation-44 (CD44) and of Neuregulin-1 Requires Substrate Dimerization. J. Biol. Chem. 290 , 17041-54, (2015) Ectodomain shedding of transmembrane precursor proteins generates numerous life-essential molecules, such as epidermal growth factor receptor ligands. This cleavage not only releases the regulatory gr... | |
| Prevention of abdominal aortic aneurysm progression by targeted inhibition of matrix metalloproteinase activity with batimastat-loaded nanoparticles. Circ. Res. 117 , e80-9, (2015) Matrix metalloproteinases (MMPs)-mediated extracellular matrix destruction is the major cause of development and progression of abdominal aortic aneurysms. Systemic treatments of MMP inhibitors have s... |
Synonyms
| (2R,3S)-N-Hydroxy-2-isobutyl-N-[(2S)-1-(methylamino)-1-oxo-3-phenylpropan-2-yl]-3-[(2-thienylsulfanyl)methyl]succinamide |
| (2R,3S)-N-hydroxy-N-[(2S)-1-(methylamino)-1-oxo-3-phenylpropan-2-yl]-2-(2-methylpropyl)-3-[(thiophen-2-ylsulfanyl)methyl]butanediamide |
| (2S,3R)-5-Methyl-3-(((aS)-a-(methylcarbamoyl)phenethyl)carbamoyl)-2-((2-thienylthio)methyl)hexanohydroxamic Acid |
| (2R,3S)-N-Hydroxy-2-isobutyl-N-[(2S)-1-(methylamino)-1-oxo-3-phenyl-2-propanyl]-3-[(2-thienylsulfanyl)methyl]succinamide |
| BB-94 |
| Butanediamide, N-hydroxy-N-[(1S)-2-(methylamino)-2-oxo-1-(phenylmethyl)ethyl]-2-(2-methylpropyl)-3-[(2-thienylthio)methyl]-, (2R,3S)- |
| Batimastat (BB-94) |
| [2R-[1(S*),2R*,3S*]]-N4-Hydroxy-N1-[2-(methylamino)-2-oxo-1-(phenylmethyl)ethyl]-2-(2-methylpropyl)-3-[(2-thienylthio)methyl]butane Diamide |
| 1rm8 |
| Batimastat |
