BB-Cl-Amidine

BB-Cl-amidine is a pan inhibitor of peptidyl arginine deiminases (PADs) and a proteolysis-resistant derivative of Cl-amidine (Cay-10599). It irreversibly inhibits PAD1-4 (kinact/KI = 16,100, 4,100, 6,800, and 13,300 M-1min-1, respectively). BB-Cl-amidine (20 and 200 µM) inhibits the formation of neutrophil extracellular traps (NETs) induced by phorbol 12-myristate 13-acetate (PMA, Cay-10008014) without altering hydrogen peroxide (H2O2) production in bone marrow-derived neutrophils. It inhibits IFN-beta production induced by the DNA virus herpes simplex virus 1 (HSV-1) but not the RNA virus Sendai virus in mouse bone marrow-derived macrophages (BMDMs) when used at a concentration of 1 µM. Ex vivo, BB-Cl-amidine (10 mg/kg) reduces BMDM IFN-beta and TNF-alpha production induced by diABZI STING agonist-1 (Cay-28054) in wild-type, Pad2-/-, and Pad4-/- mice. BB-Cl-amidine (20 mg/kg per day) increases survival, as well as reduces splenomegaly, myocarditis, and cardiac fibrosis in a Trex1D18N/D18N mouse model of Aicardi-Goutières syndrome (AGS).Formal Name: N-[(1S)-1-(1H-benzimidazol-2-yl)-4-[(2-chloro-1-iminoethyl)amino]butyl]-[1,1'-biphenyl]-4-carboxamide. CAS Number: 1802637-39-3. Molecular Formula: C26H26ClN5O. Formula Weight: 460.0. Purity: >95%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 20 mg/ml, DMSO: 20 mg/ml, Ethanol: 25 mg/ml, Ethanol:PBS(pH 7.2) (1:1): 0.5 mg/ml. lambdamax: 274, 281 nm. SMILES: O=C(N[C@@H](CCCNC(CCl)=N)C1=NC2=C(C=CC=C2)N1)C(C=C3)=CC=C3C4=CC=CC=C4. InChi Code: InChI=1S/C26H26ClN5O/c27-17-24(28)29-16-6-11-23(25-30-21-9-4-5-10-22(21)31-25)32-26(33)20-14-12-19(13-15-20)18-7-2-1-3-8-18/h1-5,7-10,12-15,23H,6,11,16-17H2,(H2,28,29)(H,30,31)(H,32,33)/t23-/m0/s1. InChi Key: YDOAWJHYHGBQFI-QHCPKHFHSA-N.