193275-84-2 Usage
Uses
Different sources of media describe the Uses of 193275-84-2 differently. You can refer to the following data:
1. Chemotherapeutic (farnesyl transfer ase inhibitor).
2. Lonafarnib is an orally bioavailable tricyclic inhibitor of farnesyl protein transferase. It inhibits Rheb farnesylation and mTOR signaling and enhances taxane and tamoxifen antitumor activity. Studies show that it induces CCAAT/enhancer-binding protein homologous protein-dependent expression of death receptor 5, leading to induction of apoptosis in human cancer cells
Definition
ChEBI: A 4-{2-[4-(3,10-dibromo-8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)piperidin-1-yl]-2-oxoethyl}piperidine-1-carboxamide that has R configuration. It is used as oral farnesyltransferase
nhibitor.
General Description
Lonafarnib (SCH66336) is a farnesyl transferase inhibitor (FTI). K- and N-Ras are substrates of farnesyl transferase.
Biological Activity
lonafarnib (sch66336, sarasar) is an potent, selective, orally, bioavailable tricyclic nonpeptidyl nonsulfhydry inhibitor of farnesyltransferase (ftase).[1] it is a small molecular with the formula of c27h31br2cln4o2 and molecular weight of 638.82. farnesylated ras proteins was found to regulate signal transduction pathways which drive cell proliferation, growth and survival and be required for its membrane localization.[1, 2] lonafarnib inhibits the post-translational farnesylcation of ras proteins, therefore blocking translocation of ras to the plasma membrane.[3][1] eric w, malcolm j. m, kim n. c, d. scott e, et al. a multinomial phase ii study of lonafarnib (sch 66336) in patients with refractory urothelial cancer. urologic oncology: seminars and original investigations. 2005, 23. 143-149.[2] gongjie l, stacey a. t, cindy h. m, yunsheng h, w. robert b, et al. continuous and intermittent dosing of lonafarnib potentiates the therapeutic efficacy of docetaxel on preclinical human prostate cancer models. int. j. cancer. 2009, 125. 2711–2720.[3] vasiliki a. n, alexander j. s, keith t. f, hensin t, et al. melanoma: new insights and new therapies. j invest dermatol. 2012, 132. 854–863.
Biochem/physiol Actions
Lonafarnib prevents the post-translational lipid modification of H-Ras and other farnesylated proteins. Lonafarnib treatment results in microtubule bundling, increased microtubule acetylation and stabilization and suppression of microtubule dynamics.
Mechanism of action
Lonafarnib is a protein farnesyltransferase inhibitor (FTI) that reversibly binds to the farnesyltransferase CAAX binding site9, thereby inhibiting progerin farnesylation and subsequent intercalation into the nuclear membrane.
Side effects
vomitingdiarrheanauseastomach painconstipationgasdecreased appetitedecreased weight
Check Digit Verification of cas no
The CAS Registry Mumber 193275-84-2 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,9,3,2,7 and 5 respectively; the second part has 2 digits, 8 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 193275-84:
(8*1)+(7*9)+(6*3)+(5*2)+(4*7)+(3*5)+(2*8)+(1*4)=162
162 % 10 = 2
So 193275-84-2 is a valid CAS Registry Number.
InChI:InChI=1/C27H31Br2ClN4O2/c28-20-12-19-2-1-18-13-21(30)14-22(29)24(18)25(26(19)32-15-20)17-5-9-33(10-6-17)23(35)11-16-3-7-34(8-4-16)27(31)36/h12-17,25H,1-11H2,(H2,31,36)/t25-/m1/s1
193275-84-2Relevant articles and documents
(+)-4-[2-[4-(8-chloro-3,10-dibromo-6,11-dihydro-5H- benzo[5,6]cyclohepta[1,2-b]pyridin-11(R)-yl)-1-piperidinyl]-2-oxo-ethyl]-1- piperidinecarboxamide (SCH-66336): A very potent farnesyl protein transferase inhibitor as a novel antitumor agent
George Njoroge,Taveras, Arthur G.,Kelly, Joseph,Remiszewski, Stacy,Mallams, Alan K.,Wolin, Ronald,Afonso, Adriano,Cooper, Alan B.,Rane, Dinananth F.,Liu, Yi-Tsung,Wong, Jesse,Vibulbhan, Bancha,Pinto, Patrick,Deskus, Jeffrey,Alvarez, Carmen S.,Del Rosario, Joycelyn,Connolly, Michael,Wang, James,Desai, Jagdish,Rossman, Randall R.,Robert Bishop,Patton, Robert,Wang, Lynn,Kirschmeier, Paul,Bryant, Mathew S.,Nomeir, Amin A.,Lin,Liu, Ming,McPhail, Andrew T.,Doll, Ronald J.,Girijavallabhan, Viyyoor M.,Ganguly, Ashit K.
, p. 4890 - 4902 (1998)
We have previously shown that appropriate modification of the benzocycloheptapyridine tricyclic ring system can provide potent farnesyl protein transferase (FPT) inhibitors with good cellular activity. Our laboratories have also established that incorporation of either pyridinylacetyl N-oxide or 4-N-carboxamidopiperidinylacetyl moieties results in pharmacokinetically stable inhibitors that are orally efficacious in nude mice. We now demonstrate that further elaboration of the tricyclic ring system by introducing a bromine atom at the 7- or the 10-position of the 3- bromo-8-chlorotricyclic ring system provides compounds that have superior potency and selectivity in FPT inhibition. These compounds have good serum levels and half-lives when given orally to rodents and primates. In vitro and in vivo evaluation of a panel of these inhibitors has led to identification of 15 (SCH 66336) as a highly potent (IC50 = 1.9 nM) antitumor agent that is currently undergoing human clinical trials.
A novel enantioselective alkylation and its application to the synthesis of an anticancer agent
Kuo, Shen-Chun,Chen, Frank,Hou, Donald,Kim-Meade, Agnes,Bernard, Charles,Liu, Jinchu,Levy, Stacy,Wu, George G.
, p. 4984 - 4987 (2007/10/03)
A novel enantioselective alkylation of double benzylic substrates with secondary electrophiles is reported. A simple norephedrine-based chiral ligand was synthesized that gives alkylation product in 95% yield and 95% ee. A unique water effect on the enantioselectivity was unveiled. Good to excellent ee values were obtained with a number of double benzylic substrates and secondary electrophiles. This novel reaction has been applied to the synthesis of a promising anticancer agent.
