A2577-1mg | Batimastat (BB-94) [130370-60-4] Clinisciences

Background

Batimastat (also known as BB-49), [4-(N-hydroxyamino)-2R-isobutyl-3S-(thiopen-2-ylthiomethyl)-succinyl-_L-phenylalanine-N-methylamide, is a potent and synthetic inhibitor of a broad spectrum of matrix metalloproteinases (MMPs), including interstitial collagenase (IC₅₀ = 3 nM), stromelysin (IC₅₀ = 20 nM), M_r 72,000 type IV collagenase (IC₅₀ = 4 nM), M_r 92,000 type IV collagenase (IC₅₀ = 4 nM), and matrilysin (IC₅₀ = 6 nM). It is a low-molecular-weight (MW = 478) and peptide-like collagen substrate analogue consisting of a peptide backbone and a hydroxamic acid group which bind to MMPs and the catalytically active zinc atom respectively. Batimastat exhibits antineoplastic and antiangiogenic activity in various tumor models, including ovarian carcinoma xegnografts and human colon tumor.

Reference

Bernard Davies, Peter D. Brown, Nick East, Michael J. Crimmin, and Frances R. Balkwill. A synthetic matrix metalloproteinase inhibitor decreases tumor burden and prolongs survival of mice bearing human ovarian carcinoma xenografts. Cancer Research 1993; 53: 2087-2091

X. Wang, X. Fu, P.D. Brown, M. J. Crimmin, and R. M. Hoffman. Matrix metalloproteinase inhibitor BB-94 (batimastat) inhibits human colon tumor growth and spread in a patient-like orthotopic model in nude mice. Cancer Research 1994; 54: 4726-4728

Raffaella Giavazzi, Angela Garofalo, Cristina Ferri, Valeria Lucchini, Elisabeth A. Bone, Stefania Chiari, Peter D. Brown, M. Ines Nicoletti, and Giulia Taraboletti. Batimastat, a synthetic inhibitor of matrix metalloproteinases, potentiates the antitumor activity of cisplatin in ovarian carcinoma xgenografts. Clinical Cancer Research 1998; 4: 985-992

Product Citation

1. Martin Baron, et al. "Alternative mechanisms of Notch activation by partitioning into distinct endosomal domains." J Cell Biol. 2024 May 6;223(5):e202211041. PMID: 38358349
2. Johannes Roessler, Dagmar Pich, et al. "SARS-CoV-2 and Epstein–Barr Virus-like Particles Associate and Fuse with Extracellular Vesicles in Virus Neutralization Tests." Biomedicines. 2023 Oct 25;11(11):2892. PMID: 38001893
3. Hui-Lam Rachel Kwan, Zora Chui-Kuen Chan, et al. "Nerve-independent formation of membrane infoldings at topologically complex postsynaptic apparatus by caveolin-3." Sci Adv. 2023 Jun 16;9(24):eadg0183. PMID: 37327338
4. Georg Jocher , Vincent Grass, et al. "ADAM10 and ADAM17 promote SARS‐CoV‐2 cell entry and spike protein‐mediated lung cell fusion." EMBO Rep. 2022 Jun 7;23(6):e54305. PMID: 35527514
5. Miri Morgulis, Mark R Winter, et al. "VEGF signaling activates the matrix metalloproteinases, MmpL7 and MmpL5 at the sites of active skeletal growth and MmpL7 regulates skeletal elongation." Dev Biol. 2021 May;473:80-89. PMID: 33577829
6. Zhijun Liu, Himani Nailwal, et al. "A class of viral inducer of degradation of the necroptosis adaptor RIPK3 regulates virus-induced inflammation." Immunity. 2021 Feb 9;54(2):247-258.e7. PMID: 33444549
7. Chan ZC, Kwan HR, et al. "Site-directed MT1-MMP trafficking and surface insertion regulate AChR clustering and remodeling at developing NMJs." Elife. 2020;9:e54379. PMID: 32208136
8. Xi Y, Huang H, et al. "Tissue inhibitor of metalloproteinase 1 suppresses growth and differentiation of osteoblasts and differentiation of osteoclasts by targeting the AKT pathway." Exp Cell Res. 2020;111930. PMID: 32113948
9. Karpova D, Rettig MP, et al. "Targeting VLA4 integrin and CXCR2 mobilizes serially repopulating hematopoietic stem cells." J Clin Invest. 2019 May 14;130:2745-2759. PMID: 31085833
10. Clarke C, Gallagher C, et al. "Transcriptomic analysis of IgG4 Fc-fusion protein degradation in a panel of clonally-derived CHO cell lines using RNASeq."Biotechnol Bioeng. 2019 Jun;116(6):1556-1562. PMID: 30802296
11. Lin CC, Kurashige M, et al. "A cleavage product of Polycystin-1 is a mitochondrial matrix protein that affects mitochondria morphology and function when heterologously expressed." Sci Rep. 2018 Feb 9;8(1):2743. PMID: 29426897
12. Lertudomphonwanit C, Mourya R, et al. "Large-scale proteomics identifies MMP-7 as a sentinel of epithelial injury and of biliary atresia." Sci Transl Med. 2017 Nov 22;9(417). PMID: 29167395
13. Kidacki M, Lehman HL, et al. "p120-Catenin Downregulation and PIK3CA Mutations Cooperate to Induce Invasion through MMP1 in HNSCC." Mol Cancer Res. 2017 Oct;15(10):1398-1409. PMID: 28637905
14. Bao JX, Zhang QF, et al. "Implication of CD38 gene in autophagic degradation of collagen I in mouse coronary arterial myocytes." Front Biosci (Landmark Ed). 2017 Jan 1;22:558-569. PMID: 27814632
15. Zhang K, Liu X, et al. "Targeting TGF-β1 inhibits invasion of anaplastic thyroid carcinoma cell through SMAD2-dependent S100A4-MMP-2/9 signalling." Am J Transl Res. 2016 May 15;8(5):2196-209. PMID: 27347327
16. Werneburg S, Buettner FF, et al. "Polysialylation and lipopolysaccharide-induced shedding of E-selectin ligand-1 and neuropilin-2 by microglia and THP-1 macrophages." Glia.2016 May 9. PMID: 27159043

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Chemical Properties

Physical Appearance	A solid
Storage	Store at 4°C
M.Wt	477.64
Cas No.	130370-60-4
Formula	C₂₃H₃₁N₃O₄S₂
Synonyms	Batimastat, BB-94
Solubility	≥23.88 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH
Chemical Name	(2S,3R)-N1-hydroxy-3-isobutyl-N4-((S)-1-(methylamino)-1-oxo-3-phenylpropan-2-yl)-2-((thiophen-2-ylthio)methyl)succinamide
SDF	Download SDF
Canonical SMILES	CNC([C@@H](NC([C@@H]([C@H](CSC1=CC=CS1)C(NO)=O)CC(C)C)=O)CC2=CC=CC=C2)=O
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.

Protocol

Cell experiment:
Cell lines	C170HM2 and AP5LV cell lines
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	96 h; 3.0 μg/mL
Applications	In vitro proliferation in the presence of batimastatwas assessed by the MTT absorbance assay. The effect of batimastat on the in vitro growth of C170HM2 and AP5LV in both serum-free and scrum-containing culture media was determined three times. Batimastat had no significant effect on the growth of either cell line.
Animal experiment:
Animal models	Orthotopic transplant model of human colon cancer in nude mice
Dosage form	30 mg/kg; i.p.
Applications	Treatment with BB-94 caused a significant reduction in the median weight of the primary tumor from 293 mg (range, 1141 to 124 mg) in the control group to 144 mg (range, 424 to 38 mg) in the BB-94 treated group (P <0.001) and resulted in a marked reduction in the incidence of tumor invasion of adjacent tissue, from 12 of 18 mice in the control group (67%) to 7 of 20 mice in the BB-94 treated group (35%).
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] Watson S A, Morris T M, Robinson G, et al. Inhibition of organ invasion by the matrix metalloproteinase inhibitor batimastat (BB-94) in two human colon carcinoma metastasis models [J]. Cancer research, 1995, 55 (16): 3629-3633. [2] Wang X, Fu X, Brown P D, et al. Matrix metalloproteinase inhibitor BB-94 (batimastat) inhibits human colon tumor growth and spread in a patient-like orthotopic model in nude mice [J]. Cancer research, 1994, 54 (17): 4726-4728.

Biological Activity

Description	Batimastat (BB-94) is a potent, broad spectrum inhibitor of matrix metalloprotease (MMP) for MMP-1, MMP-2, MMP-9, MMP-7 and MMP-3 with IC50 of 3 nM, 4 nM, 4 nM, 6 nM and 20 nM, respectively.
Targets	MMP-1	MMP-2	MMP-9	MMP-7	MMP-3
IC50	3 nM	4 nM	4 nM	6 nM	20 nM