A4050-10mg | GM 6001 [142880-36-2] Clinisciences

Background

GM 6001 is a broad-spectrum inhibitor of MMP with Ki values of 0.4nM, 0.5nM, 27nM, 0.1nM and 0.2nM, respectively for MMP-1,2,3,8 and 9 [1].

MMPs are divided into 4 subfamilies: stromelysins, gelatinases, membrane-type MMPs, and collagenases. They play major roles in mediating the effects of IL-1 during meniscal healing. As an inhibitor of MMP, GM 6001 is reported to enhance the repair of meniscal lesions in an inflammatory microenvironment. MMPs also play roles in the transactivation of EGFR induced by GPCR agonists. It is reported that treatment of GM 6001 inhibits the phosphorylation of EGFR as well as the activation of ERK induced by bombesin or LPA. The DNA synthesis induced by bombesin or LPA is also attenuated by GM 6001 since the activity of MMP is required for the GPCR-induced late response mitogenic signaling [1, 2].

References:
[1] McNulty AL, Weinberg JB, Guilak F. Inhibition of matrix metalloproteinases enhances in vitro repair of the meniscus. Clin Orthop Relat Res. 2009 Jun;467(6):1557-67.
[2] Santiskulvong C, Rozengurt E. Galardin (GM 6001), a broad-spectrum matrix metalloproteinase inhibitor, blocks bombesin- and LPA-induced EGF receptor transactivation and DNA synthesis in rat-1 cells. Exp Cell Res. 2003 Nov 1;290(2):437-46.

Product Citation

1. Wenlong Zhang, Qing Zhang, et al. "Crosstalk between IL‐15Rα+ tumor‐associated macrophages and breast cancer cells reduces CD8+ T cell recruitment." Cancer Commun (Lond). 2022 Jun;42(6):536-557. PMID: 35615815
2. Mona Nazemi. "ECM internalisation as a novel modulator of cancer cell growth/survival." The University of Sheffield. April 2021.
3. Tan Ma, Yuan Zhou, et al. "Maternal exposure to di-n-butyl phthalate promotes the formation of testicular tight junctions through downregulation of NF-#B/COX-2/PGE2/MMP-2 in mouse offspring." Environ Sci Technol. 2020 Jul 7;54(13):8245-8258. PMID: 32525310
4. Tewari BP, Chaunsali L, et al. "Perineuronal nets decrease membrane capacitance of peritumoral fast spiking interneurons in a model of epilepsy." Nat Commun. 2018 Nov 9;9(1):4724. PMID: 30413686
5. 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

Chemical Properties

Physical Appearance	A solid
Storage	Store at -20°C
M.Wt	388.46
Cas No.	142880-36-2
Formula	C₂₀H₂₈N₄O₄
Solubility	insoluble in H2O; insoluble in EtOH; ≥19.42 mg/mL in DMSO
Chemical Name	(2R)-N'-hydroxy-N-[(2S)-3-(1H-indol-3-yl)-1-(methylamino)-1-oxopropan-2-yl]-2-(2-methylpropyl)butanediamide
SDF	Download SDF
Canonical SMILES	CC(C)CC(CC(=O)NO)C(=O)NC(CC1=CNC2=CC=CC=C21)C(=O)NC
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 [1]:
Cell lines	MDA-MB-435 cells
Preparation method	Soluble in DMSO > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.
Reaction Conditions	1, 2, 4 nM; 6 or 12 h.
Applications	In MDA-MB-435 cells, GM 6001 increases the respiratory rate by 80% and [3H] thymidine incorporation by 50% when treated for 6 h and 12 h respectively, which suggest that GM 6001 increase DNA synthesis. GM 6001 also increases ERK activity and p38 kinase activity.
Animal experiment [2]:
Animal models	Rats with balloon injury of the carotid artery.
Dosage form	100 mg/kg; 2, 4, 7, 10, or 14 days; IP injection.
Preparation method	Dissolved in 4% CMC.
Applications	GM 6001 reduces the amount of SMCs that migrated into the intima by 97% at 4 days after injury and inhibits lesions growth, which is mediated by MMP. However, at 14 days after injury, intimal area and the amount of SMCs were the same in GM 6001-treated and control rats.
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]. Porter JF, Shen S, Denhardt DT. Tissue inhibitor of metalloproteinase-1 stimulates proliferation of human cancer cells by inhibiting a metalloproteinase. Br J Cancer, 2004, 90(2): 463-470. [2]. Bendeck MP, Irvin C, Reidy MA. Inhibition of matrix metalloproteinase activity inhibits smooth muscle cell migration but not neointimal thickening after arterial injury. Circ Res, 1996, 78(1): 38-43.

Biological Activity

Description	GM 6001 is a broad-spectrum inhibitor of MMP with Ki values of 0.4nM, 0.5nM, 27nM, 0.1nM and 0.2nM, for MMP-1,2,3,8 and 9, respectively.
Targets	MMP-1	MMP-2	MMP-3	MMP-8	MMP-9
IC50	0.4 nM (Ki)	0.5 nM (Ki)	27 nM (Ki)	0.1 nM (Ki)	0.2 nM (Ki)