2. Signaling Pathways
  3. Metabolic Enzyme/Protease
  4. MetAP
  5. MetAP1 Isoform

MetAP1

Methionine aminopeptidase 1 (MetAP1) catalyzes the excision of N-terminal initiator methionine (iMet) from nascent peptide chains, a critical step for proper protein maturation and post-translational modification[1][2]. Mechanistically, MetAP1 coordinates with the nascent polypeptide-associated complex and N-terminal acetyltransferase D (NatD) to cotranslationally process histones H2A and H4, ensuring chromatin integrity during S-phase[3]. Compared with the related isoform MetAP2, MetAP1 exhibits higher specificity toward N termini starting with Met-Ser, Met-Pro, and Met-Ala, which MetAP2 cannot efficiently process, highlighting non-redundant substrate preferences[1][4]. In disease models, elevated METAP1 expression in endothelial cells contributes to impaired angiogenesis and proinflammatory signaling, notably observed in preeclampsia[5]. Experimental models using METAP1 knockout or knockdown in human cell lines reveal slowed G2/M cell cycle progression and reduced proliferation, confirming its essential role in cell division[2][4]. Structurally, MetAP1 contains cytosolic and mitochondrial variants with distinct active-site conformations that accommodate specific substrates, differentiating it from MetAP2 and the mitochondrial MetAP1D isoform[6][7]. For research applications, selective MetAP1 inhibitors, including pyridinylquinazolines and bengamide derivatives, effectively target enzymatic activity in vitro and in primary cells, enabling mechanistic studies and potential therapeutic exploration[8][9]. These inhibitors demonstrate utility in probing MetAP1-dependent cell cycle regulation and protein N-terminal processing, offering precise tools for functional and pharmacological analyses[2][9].

References:

MetAP1 Related Products (3):

Cat. No. Product Name Effect Purity
  • HY-118953
    LAF389
    		Inhibitor
    LAF389, a prodrug of LAF153 (HY-183876), is a methionine aminopeptidase (MetAps) inhibitor with an IC50 of 800 nM against MetAp2, and exhibits a maximum inhibition rate of 20% against MetAp1 at 300 nM. LAF389 possesses antiproliferative, antiangiogenic and cytotoxic activities. LAF389 can be used in research related to cancers such as advanced solid tumors.
  • HY-116861
    A-357300
    		Inhibitor
    A-357300 is a reversible and selective MetAP2 inhibitor with IC50s of 0.12 and 57 μM against MetAP2 and MetAP1. A-357300 induces cytostasis by cell cycle arrest at the G1 phase selectively in endothelial cells and in a subset of tumor cells. A-357300 inhibits angiogenesis both in vitro and in vivo and shows potent antitumor efficacy in carcinoma, sarcoma, and neuroblastoma murine models. A-357300 can be used for the studies of neuroblastoma, fibrosarcoma and breast cancer.
  • HY-119062
    A-800141
    		Inhibitor
    A-800141 is an orally active, selective, sulfonamide-based MetAP2 inhibitor (IC50=12 nM) that binds reversibly to MetAP2 and interacts with its manganese ions. A-800141 induces the production of N-terminal methionine-unprocessed GAPDH variants, which in turn triggers G1-phase cell cycle arrest, elevates p21 levels, and reduces the levels of phosphorylated Rb and total cyclin A. A-800141 exhibits anti-angiogenic and tumor growth inhibitory effects, and produces synergistic effects when combined with cytotoxic inhibitors or BCL-2 inhibitors. A-800141 has been widely used in scientific research related to B-cell lymphoma, neuroblastoma, prostate cancer, colon cancer, melanoma and other fields.