Numidargistat, also known as INCB01158 and CB1158, is a potent and orally active arginase inhibitor with IC50=89 nM) . CB-1158 blocked myeloid cell-mediated suppression of T cell proliferation in vitro and reduced tumor growth in multiple mouse models of cancer, as a single agent and in combination with checkpoint blockade, adoptive T cell therapy, adoptive NK cell therapy, and the chemotherapy agent gemcitabine. CB-1158 increased tumor-infiltrating CD8+ T cells and NK cells, inflammatory cytokines, and expression of interferon-inducible genes. CB-1158 may be potentially useful in renal cell cancer, breast cancer, non-small cell lung cancer, acute myeloid leukemia, and other tumor types where arginase-secreting MDSCs are known to play an immunosuppressive role. (see ADDITIONAL INFORMATION in this web page for CB-1158 structure confusion).

 

Brand: BCM

 

Target: Arginase 2:296 nM , Arginase 1:86 nM

 

In Vitro: CB-1158 inhibits native arginase 1 (Arg1) in human granulocyte, erythrocyte, and hepatocyte lysate (IC50s: 178 nM, 116 nM, and 158 nM), and blocks Arg1 in cancer patient plasma (IC50: 122 nM). CB-1158 also exhibits potent inhibitory activity against arginase in human HepG2, K562 cell lines, and primary human hepatocytes (IC50s: 32, 139, 210 μM). CB-1158 shows no effect on NOS and not directly cytotoxic to murine cancer cell lines.

 

In Vivo: CB-1158 (100 mg/kg, p.o., twice per day) decreases the number of myeloid cells and increases tumor-infiltrating cytotoxic cells in mice. CB-1158 in combination with LY 188011 inhibits tumor growth in mice bearing CT26 cancer cells.

 

Boiling Point: 574.1±60.0 °C(Predicted)

 

pKa: 2.13±0.40(Predicted)

 

Solubility: Soluble in DMSO.

 

Isomeric SMILES: B(CCC[C@H]1CN(C[C@]1(C(=O)O)N)C(=O)[C@H](C)N)(O)O  

 

InChIKey: ZZJLMZYUGLJBSO-LAEOZQHASA-N  

 

InChI: InChI=1S/C11H22BN3O5/c1-7(13)9(16)15-5-8(3-2-4-12(19)20)11(14,6-15)10(17)18/h7-8,19-20H,2-6,13-14H2,1H3,(H,17,18)/t7-,8-,11-/m0/s1

 

Attribute
[Chem Name]	(3R,4S)-3-amino-1-[(2S)-2-aminopropanoyl]-4-(3-boronopropyl)pyrrolidine-3-carboxylic acid
[Synonym]	CB-1158; INCB01158; Numidargistat
[CAS No.]	2095732-06-0
[Formula]	C11H22BN3O5
[Molecular]	287.12
[Form]	Solid Powder
[Storage]	Sealed in dry. Stored at -20°C

Goods Tag