WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H100952
CAS#: 641571-10-0 (free base)
Description: Nilotinib, also known as AMN107, is a small-molecule tyrosine kinase inhibitor approved for the treatment of imatinib-resistant chronic myelogenous leukemia. Structurally related to imatinib, it was developed based on the structure of the Abl-imatinib complex to address imatinib intolerance and resistance. Nilotinib is a selective Bcr-Abl kinase inhibitor that is 10-30 fold more potent than imatinib in inhibiting Bcr-Abl tyrosine kinase activity and proliferation of Bcr-Abl expressing cells. Nolitinib was developed by Novartis and is sold under the trade name Tasigna.
Hodoodo Cat#: H100952
Name: Nilotinib free base
CAS#: 641571-10-0 (free base)
Chemical Formula: C28H22F3N7O
Exact Mass: 529.18
Molecular Weight: 529.530
Elemental Analysis: C, 63.51; H, 4.19; F, 10.76; N, 18.52; O, 3.02
Related CAS #: 923288-90-8 (HCl hydrate) 923288-95-3 (HCl) 641571-10-0 (free base) 923289-71-8 (hydrochloride dihydrate) 1277165-20-4 (dihydrochloride dihydrate)
Synonym: Nilotinib free base; AMN 107; AMN107; AMN-107; Nilotinib; US brand name: Tasigna.
IUPAC/Chemical Name: 4-methyl-N-(3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-{(4-(pyridin-3-yl)pyrimidin-2-yl)amino}benzamide
InChi Key: HHZIURLSWUIHRB-UHFFFAOYSA-N
InChi Code: InChI=1S/C28H22F3N7O/c1-17-5-6-19(10-25(17)37-27-33-9-7-24(36-27)20-4-3-8-32-14-20)26(39)35-22-11-21(28(29,30)31)12-23(13-22)38-15-18(2)34-16-38/h3-16H,1-2H3,(H,35,39)(H,33,36,37)
SMILES Code: O=C(NC1=CC(C(F)(F)F)=CC(N2C=C(C)N=C2)=C1)C3=CC=C(C)C(NC4=NC=CC(C5=CC=CN=C5)=N4)=C3
Appearance: White to off-white 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
Shelf Life: >2 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
More Info:
| Biological target: | Nilotinib (AMN-107) is a selective Bcr-Abl inhibitor with IC50 less than 30 nM in Murine myeloid progenitor cells. |
| In vitro activity: | Nilotinib inhibited proliferation, migration, and actin filament formation, as well as the expression of α-SMA and collagen in activated HSCs. Nilotinib induced apoptosis of HSCs, which was correlated with reduced bcl-2 expression, increased p53 expression, cleavage of PARP, as well as increased expression of PPARγ and TRAIL-R. Nilotinib also induced cell cycle arrest, accompanied by increased expression of p27 and downregulation of cyclin D1. Interestingly, Nilotinib not only inhibited activation of PDGFR, but also TGFRII through Src. Nilotinib significantly inhibited PDGF and TGFβ-simulated phosphorylation of ERK and Akt. Furthermore, PDGF- and TGFβ-activated phosphorylated form(s) of Abl in human HSCs were inhibited by Nilotinib. Reference: J Hepatol. 2011 Sep;55(3):612-625. https://linkinghub.elsevier.com/retrieve/pii/S0168-8278(11)00027-4 |
| In vivo activity: | Histopathology showed that nilotinib attenuated the extent of lung injury and fibrosis. The numbers of inflammatory cells and levels of IL-6, IL-1β and tumor necrosis factor-α were decreased in the nilotinib groups on days 3 and 7. Nilotinib therapy significantly reduced the levels of hydroxyproline on days 14 and 21, which was accompanied by decreased expression levels of transforming growth factor (TGF)-β1 and PDGFR-β. Nilotinib also significantly reduced the expression levels of the genes for TGF-β1 and platelet-derived growth factor (PDGF). When nilotinib was given 7 days after the instillation of bleomycin, it attenuated pulmonary fibrosis. Reference: Respiration. 2011;82(3):273-87. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21659722/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 2.0 | 3.80 |
The following data is based on the product molecular weight 529.53 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.
| 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 |
| Formulation protocol: | |
| In vitro protocol: | 1. Liu Y, Wang Z, Kwong SQ, Lui ELH, Friedman SL, Li FR, Lam RWC, Zhang GC, Zhang H, Ye T. Inhibition of PDGF, TGF-β, and Abl signaling and reduction of liver fibrosis by the small molecule Bcr-Abl tyrosine kinase antagonist Nilotinib. J Hepatol. 2011 Sep;55(3):612-625. doi: 10.1016/j.jhep.2010.11.035. Epub 2011 Jan 18. PMID: 21251937. |
| In vivo protocol: | 1. Rhee CK, Lee SH, Yoon HK, Kim SC, Lee SY, Kwon SS, Kim YK, Kim KH, Kim TJ, Kim JW. Effect of nilotinib on bleomycin-induced acute lung injury and pulmonary fibrosis in mice. Respiration. 2011;82(3):273-87. doi: 10.1159/000327719. Epub 2011 Jun 9. PMID: 21659722; PMCID: PMC7068797. 2. Weisberg E, Manley PW, Breitenstein W, Brüggen J, Cowan-Jacob SW, Ray A, Huntly B, Fabbro D, Fendrich G, Hall-Meyers E, Kung AL, Mestan J, Daley GQ, Callahan L, Catley L, Cavazza C, Azam M, Neuberg D, Wright RD, Gilliland DG, Griffin JD. Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl. Cancer Cell. 2005 Feb;7(2):129-41. doi: 10.1016/j.ccr.2005.01.007. Erratum in: Cancer Cell. 2005 Apr;7(4):399. Mohammed, Azam [corrected to Azam, Mohammad]. PMID: 15710326. |
1: Breccia M, Arboscello E, Bellodi A, Colafigli G, Molica M, Bergamaschi M, Massaro F, Quattrocchi L, Sarocchi M, Spallarossa P, Alimena G. Proposal for a tailored stratification at baseline and monitoring of cardiovascular effects during follow-up in chronic phase chronic myeloid leukemia patients treated with nilotinib frontline. Crit Rev Oncol Hematol. 2016 Nov;107:190-198. doi: 10.1016/j.critrevonc.2016.10.002. Review. PubMed PMID: 27823647.
2: Fujimi A, Sakamoto H, Kanisawa Y, Minami S, Nagamachi Y, Yamauchi N, Ibata S, Kato J. Pneumatosis intestinalis during chemotherapy with nilotinib in a patient with chronic myeloid leukemia who tested positive for anti-topoisomerase I antibodies. Clin J Gastroenterol. 2016 Dec;9(6):358-364. Review. PubMed PMID: 27638345.
3: Emole J, Talabi T, Pinilla-Ibarz J. Update on the management of Philadelphia chromosome positive chronic myelogenous leukemia: role of nilotinib. Biologics. 2016 Feb 26;10:23-31. doi: 10.2147/BTT.S67844. Review. PubMed PMID: 27013862; PubMed Central PMCID: PMC4777272.
4: Sekiguchi Y, Shimada A, Matsuzawa M, Imai H, Wakabayashi M, Sugimoto K, Nakamura N, Sawada T, Arita J, Komatsu N, Noguchi M. Occurrence of Carcinoma of the Pancreas Following Nilotinib Therapy for Chronic Myeloid Leukemia: Report of a Case with Review of the Literature. Turk J Haematol. 2015 Sep;32(3):257-62. doi: 10.4274/tjh.2013.0322. Review. PubMed PMID: 26376592; PubMed Central PMCID: PMC4563202.
5: Miura M. Therapeutic drug monitoring of imatinib, nilotinib, and dasatinib for patients with chronic myeloid leukemia. Biol Pharm Bull. 2015;38(5):645-54. doi: 10.1248/bpb.b15-00103. Review. PubMed PMID: 25947908.
6: Kaur S, Arora AK, Sekhon JS, Sood N. Nilotinib-induced psoriasis in a patient of chronic myeloid leukemia responding to methotrexate. Indian J Dermatol Venereol Leprol. 2015 Mar-Apr;81(2):216-8. doi: 10.4103/0378-6323.152311. Review. PubMed PMID: 25751356.
7: Weisberg E, Nonami A, Griffin JD. Combination therapy with nilotinib for drug-sensitive and drug-resistant BCR-ABL-positive leukemia and other malignancies. Arch Toxicol. 2014 Dec;88(12):2233-42. doi: 10.1007/s00204-014-1385-5. Review. PubMed PMID: 25331939.
8: Ostendorf BN, le Coutre P, Kim TD, Quintás-Cardama A. Nilotinib. Recent Results Cancer Res. 2014;201:67-80. doi: 10.1007/978-3-642-54490-3_3. Review. PubMed PMID: 24756785.
9: Capuozzo M, Ottaiano A, Nava E, Cascone S, Cinque C, Vercellone A, Scognamiglio C, Palumbo E, Iaffaioli RV. Nilotinib for the Frontline Treatment of Chronic Myeloid Leukemia Carrying the p230 Transcript: Dream or Reality? Front Oncol. 2014 Feb 3;4:17. doi: 10.3389/fonc.2014.00017. Review. PubMed PMID: 24551597; PubMed Central PMCID: PMC3910244.
10: Signorovitch J, Ayyagari R, Reichmann WM, Wu EQ, Chen L. Major molecular response during the first year of dasatinib, imatinib or nilotinib treatment for newly diagnosed chronic myeloid leukemia: a network meta-analysis. Cancer Treat Rev. 2014 Mar;40(2):285-92. doi: 10.1016/j.ctrv.2013.09.004. Review. PubMed PMID: 24112812.
11: Eadie LN, Hughes TP, White DL. Interaction of the efflux transporters ABCB1 and ABCG2 with imatinib, nilotinib, and dasatinib. Clin Pharmacol Ther. 2014 Mar;95(3):294-306. doi: 10.1038/clpt.2013.208. Review. PubMed PMID: 24107928.
12: Kanda T, Ishikawa T, Takahashi T, Nishida T. Nilotinib for treatment of gastrointestinal stromal tumors: out of the equation? Expert Opin Pharmacother. 2013 Sep;14(13):1859-67. doi: 10.1517/14656566.2013.816676. Review. PubMed PMID: 23834614.
13: Brazzelli V, Grasso V, Borroni G. Imatinib, dasatinib and nilotinib: a review of adverse cutaneous reactions with emphasis on our clinical experience. J Eur Acad Dermatol Venereol. 2013 Dec;27(12):1471-80. doi: 10.1111/jdv.12172. Review. PubMed PMID: 23611501.
14: Quintás-Cardama A, Jabbour EJ. Considerations for early switch to nilotinib or dasatinib in patients with chronic myeloid leukemia with inadequate response to first-line imatinib. Leuk Res. 2013 May;37(5):487-95. doi: 10.1016/j.leukres.2013.01.006. Review. PubMed PMID: 23391518.
15: Deadman BJ, Hopkin MD, Baxendale IR, Ley SV. The synthesis of Bcr-Abl inhibiting anticancer pharmaceutical agents imatinib, nilotinib and dasatinib. Org Biomol Chem. 2013 Mar 21;11(11):1766-800. doi: 10.1039/c2ob27003j. Review. PubMed PMID: 23247657.
16: Drucker AM, Wu S, Busam KJ, Berman E, Amitay-Laish I, Lacouture ME. Rash with the multitargeted kinase inhibitors nilotinib and dasatinib: meta-analysis and clinical characterization. Eur J Haematol. 2013 Feb;90(2):142-50. doi: 10.1111/ejh.12052. Review. PubMed PMID: 23240881.
17: Pavey T, Hoyle M, Ciani O, Crathorne L, Jones-Hughes T, Cooper C, Osipenko L, Venkatachalam M, Rudin C, Ukoumunne O, Garside R, Anderson R. Dasatinib, nilotinib and standard-dose imatinib for the first-line treatment of chronic myeloid leukaemia: systematic reviews and economic analyses. Health Technol Assess. 2012;16(42):iii-iv, 1-277. doi: 10.3310/hta16420. Review. PubMed PMID: 23134589.
18: Loveman E, Cooper K, Bryant J, Colquitt JL, Frampton GK, Clegg A. Dasatinib, high-dose imatinib and nilotinib for the treatment of imatinib-resistant chronic myeloid leukaemia: a systematic review and economic evaluation. Health Technol Assess. 2012;16(23):iii-xiii, 1-137. doi: 10.3310/hta16230. Review. PubMed PMID: 22564553; PubMed Central PMCID: PMC4781455.
19: Rogers G, Hoyle M, Thompson Coon J, Moxham T, Liu Z, Pitt M, Stein K. Dasatinib and nilotinib for imatinib-resistant or -intolerant chronic myeloid leukaemia: a systematic review and economic evaluation. Health Technol Assess. 2012;16(22):1-410. doi: 10.3310/hta16220. Review. PubMed PMID: 22551803; PubMed Central PMCID: PMC4781389.
20: Tran A, Tawbi HA. A potential role for nilotinib in KIT-mutated melanoma. Expert Opin Investig Drugs. 2012 Jun;21(6):861-9. doi: 10.1517/13543784.2012.679341. Review. PubMed PMID: 22500535.
1. Kuo YC, Tsai HC, Rajesh R. Glutathione Liposomes Carrying Ceftriaxone, FK506, and Nilotinib to Control Overexpressed Dopamine Markers and Apoptotic Factors in Neurons. ACS Biomater Sci Eng. 2021 Jul 12;7(7):3242-3255. doi: 10.1021/acsbiomaterials.1c00555. Epub 2021 Jun 30. PMID: 34189904.
