bi 99179 bi 99179 bi 99179 is a selective small molecule inhibitor suitable for the in vivo validation of type 1 fatty acid synthase (fas) as a therapeutic target for lipid metabolism-related disorders (lipid metabolism disorder) which has been discovered by boehringer ingelheim. 3d model of bi 99179 bi 99179 names iupac name (1r,3s)-n--n-methyl-3-(propanoylamino)cyclopentane-1-carboxamide identifiers cas number 1291779-76-4 3d model (jsmol) interactive image chembl chembl1834184 chemspider 26616821 pubchem cid 51346964 unii s2jb42bbp5 y inchi inchi=1s/c23h25n3o3/c1-3-21(27)24-17-11-8-16(14-17)23(28)26(2)18-12-9-15(10-13-18)22-25-19-6-4-5-7-20(19)29-22/h4-7,9-10,12-13,16-17h,3,8,11,14h2,1-2h3,(h,24,27)/t16-,17+/m1/s1key: ynfdigjkjpnffd-sjorkvtesa-n smiles ccc(=o)n1cc(c1)c(=o)n(c)c2=cc=c(c=c2)c3=nc4=cc=cc=c4o3 properties chemical formula c23h25n3o3 molar mass 391.471 g·mol−1 pharmacology pharmacokinetics: bioavailability 46% protein binding 97.6% (rat) except where otherwise noted, data are given for materials in their standard state (at 25 °c , 100 kpa). infobox references summary bi 99179 is characterized by its high potency, high selectivity, and significant exposure (both peripheral and central) upon oral administration in rats. target information mammalian type i fas is a multi-enzyme protein that catalyzes fatty acid synthesis. it mediates key roles in neoplastic lipogenesis and is highly expressed in lipogenic tissues. while most tissues, except liver and adipose tissue, have low levels of fas expression and activity, fas is over-expressed in many cancers. accumulating evidence suggests that it is a metabolic oncogene with an important role in tumor growth and survival, thus making it an attractive target for cancer therapy. in addition to its role in oncology, fas inhibition could also represent an attractive therapeutic target in obesity; both systemic and intracerebroventricular treatment of mice with fas inhibitors led to inhibition of feeding and dramatic weight loss. moreover, inhibitors of fas have been reported to reduce the production of sebum in sebocytes; therefore, topical fas inhibition could be a potential anti-acne approach. fas consists of two identical subunits, each comprising an acyl carrier protein (acp) domain and six different catalytic domains. bi 99179 is likely to bind to the ketoacyl reductase (kr) domain (evidence: boehringer ingelheim enzymatic data and analogy to the published co-crystal structure of the human kr domain with gsk2194069). in vitro activity bi 99179 inhibits the fas enzyme isolated from hela cells with a half maximal inhibitory concentration (ic50) of 79 nm. in vitro activity probe name bi 99179 inhibition of fasn* (ic50) 79 inhibition of acetate incorporation§ mouse n-42 cells (ic50) 570 inhibition of acetate incorporation§ hum. h1975 cells (ic50) 180 cytotoxicity (ldh release from u937 cells) (ic50) >30000 *human fas enzyme isolated from hela cells. §cells incubated with compound for 1 hour, 14c-acetate in krebs–ringer buffer incubation for 4 hours, methanol:chcl3 1:1 extraction, measurement in ß-counter. fasn, fatty acid synthase; ldh, lactate dehydrogenase. in vitro dmpk and cmc probe name bi 99179 aqueous solubility @ ph 7 >39 caco permeability @ph7.4 94 caco efflux ratio 0.9 microsomal stability – rat, human <27 plasma protein binding rat 97.6 in vivo dmpk in vivo dmpk parameters probe name bi 99179 t½ (h) 3.0 tmax (h) 0.5 cmax (nm) 2110 auc0–inf (nmh) 9350 f (%) 46 cl (ml/min/kg) 8.2 vss (l/kg) 1.6 cbrain,2h (nm) 1300 ccsf,2h (nm) 50 pharmacokinetic parameters of bi 99179 in male wistar hannover rats. *fasted upon oral application of 4 mg/kg. in vivo pharmacology bi 99179 showed acute efficacy in rat models. increased hypothalamic malonyl-coa concentrations (10 or 100 mg/kg); 2 hours/24 hours post dose (p.d.) decreased cumulative food intake 100 mg/kg; 24 hours p.d. selectivity a screen covering 30 targets was reported: <20% inhibition at 10 μm for all targets.