Tipifarnib
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MedKoo CAT#: 202930

CAS#: 192185-72-1

Description: Tipifarnib, also known as R115777, is a farnesyltransferase inhibitor that is being investigated in patients 65 years of age and older with newly diagnosed acute myeloid leukemia (AML). It inhibits the Ras kinase in a post translational modification step before the kinase pathway becomes hyperactive. It inhibits prenylation of the CxxX tail motif, which allows Ras to bind to the membrane where it is active. Without this step the protein cannot function.


Chemical Structure

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Tipifarnib
CAS# 192185-72-1

Theoretical Analysis

MedKoo Cat#: 202930
Name: Tipifarnib
CAS#: 192185-72-1
Chemical Formula: C27H22Cl2N4O
Exact Mass: 488.11707
Molecular Weight: 489.4
Elemental Analysis: C, 66.26; H, 4.53; Cl, 14.49; N, 11.45; O, 3.27

Size Price Shipping out time Quantity
10mg USD 190 Same day
25mg USD 350 Same day
50mg USD 550 Same day
100mg USD 950 Same day
200mg USD 1450 Same day
500mg USD 2450 Same day
1g USD 3650 2 Weeks
2g USD 6450 2 Weeks
Inquire bulk and customized quantity

Pricing updated 2021-03-09. Prices are subject to change without notice.

Tipifarnib, purity > 98%, is in stock.The same day shipping out after order is received.

Synonym: R115777; R 115777; R-115777; LX81; NSC702818; D03720; Tipifarnib; trade name Zarnestra

IUPAC/Chemical Name: (R)-6-(Amino(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl)-4-(3-chlorophenyl)-1-methyl-2(1H)-quinolinone

InChi Key: PLHJCIYEEKOWNM-HHHXNRCGSA-N

InChi Code: InChI=1S/C27H22Cl2N4O/c1-32-16-31-15-25(32)27(30,18-6-9-20(28)10-7-18)19-8-11-24-23(13-19)22(14-26(34)33(24)2)17-4-3-5-21(29)12-17/h3-16H,30H2,1-2H3/t27-/m1/s1

SMILES Code: O=C1N(C)C2=C(C=C([C@@](C3=CC=C(Cl)C=C3)(N)C4=CN=CN4C)C=C2)C(C5=CC=CC(Cl)=C5)=C1

Appearance:
Solid powder

Purity:
>98% (or refer to the Certificate of Analysis)

Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition:
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility:
Soluble in DMSO, not in water

Shelf Life:
>5 years if stored properly

Drug Formulation:
This drug may be formulated in DMSO

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code:
2934.99.9001

Preparing Stock Solutions

The following data is based on the product molecular weight 489.4 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Select a batch to recalculate based on the batch molecular weight:
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL

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  1: Margolin KA, Moon J, Flaherty LE, Lao CD, Akerley WL 3rd, Othus M, Sosman JA, Kirkwood JM, Sondak VK. Randomized Phase II Trial of Sorafenib with Temsirolimus or Tipifarnib in Untreated Metastatic Melanoma (S0438). Clin Cancer Res. 2012 Feb 7. [Epub ahead of print] PubMed PMID: 22228638.

2: Ruchlemer R. Two genes, tipifarnib, and AML. Blood. 2012 Jan 5;119(1):2-3. PubMed PMID: 22223817.

3: Krzykowska-Petitjean K, Małecki J, Bentke A, Ostrowska B, Laidler P. Tipifarnib and tanespimycin show synergic proapoptotic activity in U937 cells. J Cancer Res Clin Oncol. 2011 Dec 31. [Epub ahead of print] PubMed PMID: 22209975.

4: Karp JE, Vener TI, Raponi M, Ritchie EK, Smith BD, Gore SD, Morris LE, Feldman EJ, Greer JM, Malek S, Carraway HE, Ironside V, Galkin S, Levis MJ, McDevitt MA, Roboz GR, Gocke CD, Derecho C, Palma J, Wang Y, Kaufmann SH, Wright JJ, Garret-Mayer E. Multi-institutional phase 2 clinical and pharmacogenomic trial of tipifarnib plus etoposide for elderly adults with newly diagnosed acute myelogenous leukemia. Blood. 2012 Jan 5;119(1):55-63. Epub 2011 Oct 14. PubMed PMID: 22001391.

5: Bai F, Villagra AV, Zou J, Painter JS, Connolly K, Blaskovich MA, Sokol L, Sebti S, Djeu JY, Loughran TP, Wei S, Sotomayor E, Epling-Burnette P. Tipifarnib-mediated suppression of T-bet-dependent signaling pathways. Cancer Immunol Immunother. 2011 Oct 9. [Epub ahead of print] PubMed PMID: 21983879.

6: Witzig TE, Tang H, Micallef IN, Ansell SM, Link BK, Inwards DJ, Porrata LF, Johnston PB, Colgan JP, Markovic SN, Nowakowski GS, Thompson CA, Allmer C, Maurer MJ, Gupta M, Weiner G, Hohl R, Kurtin PJ, Ding H, Loegering D, Schneider P, Peterson K, Habermann TM, Kaufmann SH. Multi-institutional phase 2 study of the farnesyltransferase inhibitor tipifarnib (R115777) in patients with relapsed and refractory lymphomas. Blood. 2011 Nov 3;118(18):4882-9. Epub 2011 Jul 1. PubMed PMID: 21725056; PubMed Central PMCID: PMC3208296.

7: Kirschbaum MH, Synold T, Stein AS, Tuscano J, Zain JM, Popplewell L, Karanes C, O'Donnell MR, Pulone B, Rincon A, Wright J, Frankel P, Forman SJ, Newman EM. A phase 1 trial dose-escalation study of tipifarnib on a week-on, week-off schedule in relapsed, refractory or high-risk myeloid leukemia. Leukemia. 2011 Oct;25(10):1543-7. doi: 10.1038/leu.2011.124. Epub 2011 May 31. PubMed PMID: 21625235; PubMed Central PMCID: PMC3165084.

8: Marcuzzi A, De Leo L, Decorti G, Crovella S, Tommasini A, Pontillo A. The farnesyltransferase inhibitors tipifarnib and lonafarnib inhibit cytokines secretion in a cellular model of mevalonate kinase deficiency. Pediatr Res. 2011 Jul;70(1):78-82. PubMed PMID: 21430599.

9: Yanamandra N, Buzzeo RW, Gabriel M, Hazlehurst LA, Mari Y, Beaupre DM, Cuevas J. Tipifarnib-induced apoptosis in acute myeloid leukemia and multiple myeloma cells depends on Ca2+ influx through plasma membrane Ca2+ channels. J Pharmacol Exp Ther. 2011 Jun;337(3):636-43. Epub 2011 Mar 4. PubMed PMID: 21378206; PubMed Central PMCID: PMC3101005.

10: Haas-Kogan DA, Banerjee A, Poussaint TY, Kocak M, Prados MD, Geyer JR, Fouladi M, Broniscer A, Minturn JE, Pollack IF, Packer RJ, Boyett JM, Kun LE. Phase II trial of tipifarnib and radiation in children with newly diagnosed diffuse intrinsic pontine gliomas. Neuro Oncol. 2011 Mar;13(3):298-306. PubMed PMID: 21339191; PubMed Central PMCID: PMC3064607.

11: Hong DS, Cabanillas ME, Wheler J, Naing A, Tsimberidou AM, Ye L, Waguespack SG, Hernandez M, El Naggar AK, Bidyasar S, Wright J, Sherman SI, Kurzrock R, Busaidy NL. Inhibition of the Ras/Raf/MEK/ERK and RET kinase pathways with the combination of the multikinase inhibitor sorafenib and the farnesyltransferase inhibitor tipifarnib in medullary and differentiated thyroid malignancies. J Clin Endocrinol Metab. 2011 Apr;96(4):997-1005. Epub 2011 Feb 2. Erratum in: J Clin Endocrinol Metab. 2011 Jul;96(7):2286. Busaidy, Naifa L [added]; El Naggar, Alder K [corrected to El Naggar, Adel K]. PubMed PMID: 21289252; PubMed Central PMCID: PMC3070247.

12: Lancet JE, Duong VH, Winton EF, Stuart RK, Burton M, Zhang S, Cubitt C, Blaskovich MA, Wright JJ, Sebti S, Sullivan DM. A phase I clinical-pharmacodynamic study of the farnesyltransferase inhibitor tipifarnib in combination with the proteasome inhibitor bortezomib in advanced acute leukemias. Clin Cancer Res. 2011 Mar 1;17(5):1140-6. Epub 2011 Jan 13. PubMed PMID: 21233404; PubMed Central PMCID: PMC3049960.

13: Jabbour E, Kantarjian H, Ravandi F, Garcia-Manero G, Estrov Z, Verstovsek S, O'Brien S, Faderl S, Thomas DA, Wright JJ, Cortes J. A phase 1-2 study of a farnesyltransferase inhibitor, tipifarnib, combined with idarubicin and cytarabine for patients with newly diagnosed acute myeloid leukemia and high-risk myelodysplastic syndrome. Cancer. 2011 Mar 15;117(6):1236-44. doi: 10.1002/cncr.25575. Epub 2010 Oct 19. PubMed PMID: 20960519.

14: Nghiemphu PL, Wen PY, Lamborn KR, Drappatz J, Robins HI, Fink K, Malkin MG, Lieberman FS, DeAngelis LM, Torres-Trejo A, Chang SM, Abrey L, Fine HA, Demopoulos A, Lassman AB, Kesari S, Mehta MP, Prados MD, Cloughesy TF; North American Brain Tumor Consortium. A phase I trial of tipifarnib with radiation therapy, with and without temozolomide, for patients with newly diagnosed glioblastoma. Int J Radiat Oncol Biol Phys. 2011 Dec 1;81(5):1422-7. Epub 2010 Oct 8. PubMed PMID: 20934264; PubMed Central PMCID: PMC3020272.

15: Widemann BC, Arceci RJ, Jayaprakash N, Fox E, Zannikos P, Goodspeed W, Goodwin A, Wright JJ, Blaney SM, Adamson PC, Balis FM. Phase 1 trial and pharmacokinetic study of the farnesyl transferase inhibitor tipifarnib in children and adolescents with refractory leukemias: a report from the Children's Oncology Group. Pediatr Blood Cancer. 2011 Feb;56(2):226-33. doi: 10.1002/pbc.22775. Epub 2010 Sep 21. PubMed PMID: 20860038; PubMed Central PMCID: PMC3271115.

16: David E, Kaufman JL, Flowers CR, Schafer-Hales K, Torre C, Chen J, Marcus AI, Sun SY, Boise LH, Lonial S. Tipifarnib sensitizes cells to proteasome inhibition by blocking degradation of bortezomib-induced aggresomes. Blood. 2010 Dec 9;116(24):5285-8. Epub 2010 Sep 15. PubMed PMID: 20844234.

17: Kraus JM, Tatipaka HB, McGuffin SA, Chennamaneni NK, Karimi M, Arif J, Verlinde CL, Buckner FS, Gelb MH. Second generation analogues of the cancer drug clinical candidate tipifarnib for anti-Chagas disease drug discovery. J Med Chem. 2010 May 27;53(10):3887-98. PubMed PMID: 20429511; PubMed Central PMCID: PMC2877169.

18: Biagi C, Astolfi A, Masetti R, Serravalle S, Franzoni M, Chiarini F, Melchionda F, Pession A. Pediatric early T-cell precursor leukemia with NF1 deletion and high-sensitivity in vitro to tipifarnib. Leukemia. 2010 Jun;24(6):1230-3. Epub 2010 Apr 29. PubMed PMID: 20428205.

19: Epling-Burnette PK, Loughran TP Jr. Suppression of farnesyltransferase activity in acute myeloid leukemia and myelodysplastic syndrome: current understanding and recommended use of tipifarnib. Expert Opin Investig Drugs. 2010 May;19(5):689-98. Review. PubMed PMID: 20402600; PubMed Central PMCID: PMC3252817.

20: Dalenc F, Doisneau-Sixou SF, Allal BC, Marsili S, Lauwers-Cances V, Chaoui K, Schiltz O, Monsarrat B, Filleron T, Renée N, Malissein E, Meunier E, Favre G, Roché H. Tipifarnib plus tamoxifen in tamoxifen-resistant metastatic breast cancer: a negative phase II and screening of potential therapeutic markers by proteomic analysis. Clin Cancer Res. 2010 Feb 15;16(4):1264-71. Epub 2010 Feb 9. PubMed PMID: 20145184.



Additional Information

For treatment of progressive plexiform neurofibromas associated with Neurofibromatosis type I, it successfully passed phase one clinical trials but was suspended (NCT00029354) in phase two. The compound was discovered by and is under investigation by Johnson & Johnson Pharmaceutical Research & Development, L.L.C, with registration number R115777. Tipifarnib was submitted to the FDA by Johnson & Johnson for the treatment of AML in patients aged 65 and over with a New Drug Application (NDA) to the Food and Drug Administration (FDA) on January 24, 2005. In June 2005, the FDA issued a "not approvable" letter for tipifarnib.