cl-amidine

Cl-amidine is an orally active inhibitor of peptidyl arginine deiminase (PAD) with IC50 values of 0.8 μM, 6.2 μM, and 5.9 μM for PAD1, PAD3, and PAD4, respectively. It induces apoptosis in cancer cells.

D-Cl-amidine is an effective and highly selective PAD1 inhibitor. D-Cl-amidine has a good correlation and no obvious toxicity.

Cl-amidine hydrochloride is an orally available PAD inhibitor that blocks histone 3 deimination and neutrophil extracellular trap formation and improves survival in septic mice. It induces apoptosis in cancer cells and induces miR-16 to cause cell cycle arrest.

Cl-amidine TFA is an orally active inhibitor of peptidyl arginine deminase (PAD) with IC50 values of 0.8 μM, 6.2 μM, and 5.9 μM for PAD1, PAD3, and PAD4, respectively. Cl-amidine induces apoptosis in cancer cells.

D-Cl-amidine hydrochloride, a potent and highly selective inhibitor of PAD1, exhibits excellent tolerance and does not induce significant toxicity [1].

BB-Cl-Amidine hydrochloride is an inhibitor of peptidylarginine deminase (PAD) [1].

N-[1-(Aminocarbonyl)-4-[(2-chloro-1-iminoethyl)amino]butyl]benzamide is a racemic form of Cl-amidine (S enantiomer). Cl-amidine is an orally active peptidylarginine deminase (PAD) inhibitor.

Photoswitchable PAD inhibitor is a photoactivated protein arginine deiminase (PAD) inhibitor and a derivative of BB-Cl-amidine that contains an azobenzene photoswitch allowing optical control of PAD activity.1 Without photoactivation, it is a weak inhibitor of PAD2 (IC50 = >100 μM) and is less potent than BB-Cl-amidine in inhibiting citrulline production in vitro (kinact/KIs = 2,300, 600, 1,000, and 10,510 M-1min-1 for PAD1-4, respectively) and does not inhibit histone H3 citrullination in HEK293T cells overexpressing PAD2 when used at concentrations up to 100 μM. However, it can rapidly be photoactivated with UV-A radiation to the more active cis-isomer, which is an irreversible, competitive inhibitor of histone H3 citrullination with an IC50 value of 9.1 μM.References1. Mondal, S., Parelkar, S.S., Nagar, M., et al. Photochemical control of protein arginine deiminase (PAD) activity. ACS Chem. Biol. 13(4), 1057-1065 (2018). Photoswitchable PAD inhibitor is a photoactivated protein arginine deiminase (PAD) inhibitor and a derivative of BB-Cl-amidine that contains an azobenzene photoswitch allowing optical control of PAD activity.1 Without photoactivation, it is a weak inhibitor of PAD2 (IC50 = >100 μM) and is less potent than BB-Cl-amidine in inhibiting citrulline production in vitro (kinact/KIs = 2,300, 600, 1,000, and 10,510 M-1min-1 for PAD1-4, respectively) and does not inhibit histone H3 citrullination in HEK293T cells overexpressing PAD2 when used at concentrations up to 100 μM. However, it can rapidly be photoactivated with UV-A radiation to the more active cis-isomer, which is an irreversible, competitive inhibitor of histone H3 citrullination with an IC50 value of 9.1 μM. References1. Mondal, S., Parelkar, S.S., Nagar, M., et al. Photochemical control of protein arginine deiminase (PAD) activity. ACS Chem. Biol. 13(4), 1057-1065 (2018).

BB-Cl-Yne is a cell-permeable derivative of the protein arginine deiminase (PAD) inhibitor BB-Cl-amidine that contains an alkyne moiety for use in click chemistry reactions. BB-CL-Yne inhibits PAD1-4 with Kinact/KI values of 6,400, 3,600, 10,800, and 4,900 M-1min-1, respectively. It has been used for labeling PADs in cell-free and cell-based assays, followed by click reactions with azide-modified TAMRA or biotin reporters.

LB244, a homologue of BB-Cl-amidine, functions as an orally effective STING inhibitor with an EC50 value of 0.8 μM, applicable in the treatment of STING-dependent inflammatory diseases. However, pharmacokinetic studies have shown that LB244 exhibits limited oral activity in mice [1].

YW3-56 is a potent peptidylarginine deiminase (PAD) inhibitor, with an IC50 of 1-5 μM for PAD4. Compared with Cl-amidine, YW3-56 shows >60-fold increase in cell growth inhibition efficacy (IC50 about 2.5 μM) but only 5-fold increase in PAD4 inhibition (IC sub>50 about 1-5 μM). At 2-4 μM concentrations, YW3-56 displays mainly cytostatic effects by slowing cell division, whereas at higher concentrations, it exerts cytotoxic effects by altering cell morphology and killing cells[1]. [1]. Wang Y, et al. Anticancer peptidylarginine deiminase (PAD) inhibitors regulate the autophagy flux and t he mammalian target of rapamycin complex 1 activity. J Biol Chem. 2012 Jul 27;287(31):25941-53.