Nilotinib (AMN-107) - Moligand™, 10mM in DMSO , Inhibitor of ABL proto-oncogene 1; non-receptor tyrosine kinase;Inhibitor of discoidin domain receptor tyrosine kinase 1;Inhibitor of discoidin domain receptor tyrosine kinase 2, CAS No.641571-10-0, Inhibitor of ABL proto-oncogene 1; non-receptor tyrosine kinase;Inhibitor of discoidin domain receptor tyrosine kinase 1;Inhibitor of discoidin domain receptor tyrosine kinase 2

CAS: 641571-10-0 Cat. No.: N408607 Peso molecular: 529.53 Número EC: 700-544-5

GRADE & PURITY Moligand™, 10mM in DMSO

Synonyms

4-methyl-N-(3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-(4-(pyridin-3-yl)pyrimidin-2-ylamino)benzamide

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Descripción general

Information

Nilotinib (AMN-107) Nilotinib (AMN-107) is a selective Bcr-Abl inhibitor with IC50 less than 30 nM in Murine myeloid progenitor cells. Nilotinib induces autophagy through AMPK activition.
In vitro

Nilotinib inhibits proliferation, migration, and actin filament formation, as well as the expression of α-SMA and collagen in activated HSCs. Nilotinib induces apoptosis of HSCs, which is correlated with reduced bcl-2 expression, increases p53 expression, cleavage of PARP, as well as increases expression of PPARγ and TRAIL-R. Nilotinib also induces cell cycle arrest, accompanied by increased expression of p27 and downregulation of cyclin D1. Interestingly, Nilotinib not only inhibits activation of PDGFR, but also TGFRII through Src. Nilotinib significantly inhibits PDGF and TGFβ-simulated phosphorylation of ERK and Akt. Furthermore, PDGF- and TGFβ-activated phosphorylated form(s) of Abl in human HSCs are inhibited by Nilotinib. Nilotinib inhibits most imatinib-resistant Bcr-Abl mutations, except for T315I. Nilotinib inhibits PDGF-DD-mediated ERK1/2 activation, basal and PDGF-DD-mediated activation of PDGFRβ and Akt, and schwannoma proliferation. Nilotinib is more potent than imatinib, exerting its maximal inhibitory effect at concentrations lower than steady-state trough plasma levels. Nilotinib also significantly reduces the expression levels of the genes for TGF-β1 and platelet-derived growth factor (PDGF). Nilotinib treatment also significantly inhibits the PDGF-induced proliferation of lung fibroblasts. Nilotinib inhibits the proliferation of Ba/F3 cells expressing p210- and p190-Bcr-Abl, or K562 and Ku-812F cells with IC50 values ≤12 nM.

In vivo

Nilotinib reduces collagen deposition and α-SMA expression in CCl₄ and BDL-induced fibrosis. Nilotinib could induce HSC undergoing apoptosis, which is correlated with downregulation of bcl-2. Nilotinib attenuates the extent of lung injury and fibrosis. Nilotinib therapy significantly reduces the levels of hydroxyproline on days 14 and 21, which is accompanied by decreased expression levels of transforming growth factor (TGF)-β1 and PDGFRβ. AMN107 prolongs survival of mice injected with Bcr-Abl-transformed hematopoietic cell lines or primary marrow cells, and prolongs survival in imatinib-resistant CML mouse models.
Cell Data

cell lines：

Concentrations：1-10 μM

Incubation Time：72 hours

Powder Purity:≥99%

Specifications

Sinónimos

4-methyl-N-(3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-(4-(pyridin-3-yl)pyrimidin-2-ylamino)benzamide

Especificaciones y pureza

Moligand™, 10mM in DMSO

Mecanismos bioquímicos y fisiológicos

Nilotinib (AMN-107) is a selective Bcr-Abl inhibitor with IC50 less than 30 nM in Murine myeloid progenitor cells. Nilotinib induces autophagy through AMPK activition.

Condiciones de almacenamiento de almacenamiento

Store at -80°C

Enviado en

Dry ice packs + Cold packs

Este producto requiere envío en cadena de frío. Los servicios terrestres y otros servicios económicos no están disponibles.

Grado

Moligand™

Tipo de acción

INHIBITOR

Mecanismo de acción

Inhibitor of ABL proto-oncogene 1; non-receptor tyrosine kinase;Inhibitor of discoidin domain receptor tyrosine kinase 1;Inhibitor of discoidin domain receptor tyrosine kinase 2

Nombres e identificadores

• Isómeros SMILES: CC1=C(C=C(C=C1)C(=O)NC2=CC(=CC(=C2)C(F)(F)F)N3C=C(N=C3)C)NC4=NC=CC(=N4)C5=CN=CC=C5
• Peso molecular: 529.53
• Reaxy-Rn: 10737140
• Reaxys-RN_link_address: https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=10737140&ln=

Objetivos asociados (humanos)

CYP3A4 Tclin Cytochrome P450 3A4 (1 Activities)

Discover Target: CYP3A4

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

DDR2 Tchem Discoidin domain-containing receptor 2 (6 Activities)

Discover Target: DDR2

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

DDR1 Tchem Epithelial discoidin domain-containing receptor 1 (3 Activities)

Discover Target: DDR1

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

ILK Tchem Integrin-linked protein kinase (1 Activities)

Discover Target: ILK

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

PDGFRB Tclin Platelet-derived growth factor receptor beta (2 Activities)

Discover Target: PDGFRB

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

CA6 Tclin Carbonic anhydrase 6 (1 Activities)

Discover Target: CA6

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

CA1 Tclin Carbonic anhydrase 1 (1 Activities)

Discover Target: CA1

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

CA3 Tclin Carbonic anhydrase 3 (1 Activities)

Discover Target: CA3

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

CA2 Tclin Carbonic anhydrase 2 (1 Activities)

Discover Target: CA2

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

CA4 Tclin Carbonic anhydrase 4 (1 Activities)

Discover Target: CA4

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

CA12 Tclin Carbonic anhydrase 12 (1 Activities)

Discover Target: CA12

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

CA14 Tclin Carbonic anhydrase 14 (1 Activities)

Discover Target: CA14

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

CA9 Tclin Carbonic anhydrase 9 (1 Activities)

Discover Target: CA9

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

CA7 Tclin Carbonic anhydrase 7 (1 Activities)

Discover Target: CA7

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

BCR Tclin Breakpoint cluster region protein (1 Activities)

Discover Target: BCR

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

ABL2 Tchem Tyrosine-protein kinase ABL2 (1 Activities)

Discover Target: ABL2

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

ABL1 Tclin Tyrosine-protein kinase ABL1 (21 Activities)

Discover Target: ABL1

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

KIT Tclin Mast/stem cell growth factor receptor Kit (4 Activities)

Discover Target: KIT

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

KCNH2 Tclin Potassium voltage-gated channel subfamily H member 2 (2 Activities)

Discover Target: KCNH2

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

NQO2 Tchem Ribosyldihydronicotinamide dehydrogenase [quinone] (1 Activities)

Discover Target: NQO2

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

MAP3K20 Tchem Mitogen-activated protein kinase kinase kinase 20 (1 Activities)

Discover Target: MAP3K20

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

Propiedades químicas y físicas

• Índice de refracción: 1.65
• Punto de fusión (°C): 230-242℃

Referencias

1. Xiaofei Zhang, Mengyuan Lv, Yuyang Wang, Nan Zhang, Di Chen.  (2025)  Inner-wall biochar-coated pipette tip microextraction for rapid and sustainable determination of tyrosine kinase inhibitors in plasma.  RSC Advances,  15  (40): (33536-33548).  [PMID:40959299] [10.1039/D5RA05405B]

2. Yutao Lou, Zhiyong Sun, Yitao Chai, Hui Qin, Qing Hu, Yujia Liu, Xiaowei Zheng, Ying Hu, Meihua Bao, Jinping Gu, Yiwen Zhang.  (2023)  Simultaneous quantification of donafenib, sorafenib, and their N-oxide metabolites in rat plasma using a HPLC-MS/MS method.  JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES,      [PMID:37717473] [10.1016/j.jchromb.2023.123871]

3. Yutao Lou, Mengting Cheng, Qin Cao, Kening Li, Hui Qin, Meihua Bao, Yuan Zhang, Sisi Lin, Yiwen Zhang.  (2023)  Simultaneous quantification of mirabegron and vibegron in human plasma by HPLC-MS/MS and its application in the clinical determination in patients with tumors associated with overactive bladder.  JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,      [PMID:38198885] [10.1016/j.jpba.2023.115937]

4. Fangjun Chen, Wenda Chen, Zhenxin Wang, Yingfei Peng, Beili Wang, Baishen Pan, Wei Guo.  (2023)  Development and clinical application of a liquid chromatography-tandem mass spectrometry-based assay to quantify eight tyrosine kinase inhibitors in human plasma.  Journal of Mass Spectrometry and Advances in the Clinical Lab,      [PMID:37234251] [10.1016/j.jmsacl.2023.05.001]

5. Yutao Lou, Hui Qin, Qing Hu, Yitao Chai, Hongying Zhou, Mengting Chen, Qiyue Wang, Ping Huang, Jinping Gu, Yiwen Zhang.  (2022)  Development and validation of a novel LC-MS/MS method for simultaneous quantitative determination of tyrosine kinase inhibitors in human plasma.  JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES,      [PMID:35932695] [10.1016/j.jchromb.2022.123394]

6. Wei Jingyao, Liu Ruijuan, Zhang Jiali, Liu Shuaibing, Yan Dan, Wen Xueqian, Tian Xin.  (2021)  Baicalin Enhanced Oral Bioavailability of Sorafenib in Rats by Inducing Intestine Absorption.  Frontiers in Pharmacology,      [PMID:34819863] [10.3389/fphar.2021.761763]

7. Zhao-Yang Wang, Hai-Long Wu, Yue-Yue Chang, Tong Wang, Wei Chen, Gao-Yan Tong, Ru-Qin Yu.  (2021)  Simultaneous determination of nine tyrosine kinase inhibitors in three complex biological matrices by using high-performance liquid chromatography–diode array detection combined with a second-order calibration method.  JOURNAL OF SEPARATION SCIENCE,  44  (21): (3914-3923).  [PMID:34463059] [10.1002/jssc.202100293]

8. Rubin Cheng, Yilan Huang, Yun Fang, Qirui Wang, Meixiu Yan, Yuqing Ge.  (2021)  Cryptotanshinone enhances the efficacy of Bcr-Abl tyrosine kinase inhibitors via inhibiting STAT3 and eIF4E signalling pathways in chronic myeloid leukaemia.  PHARMACEUTICAL BIOLOGY,      [PMID:34214017] [10.1080/13880209.2021.1944224]

9. Hui Lv, Juanjuan Wang, Mingying Wang, Li Shen, Ling Xiao, Taijie Chen, Tingzhe Sun, Wenjuan Li, Liangliang Zhu, Xiaoke Zhang.  (2021)  Potent inhibition of tributyltin (TBT) and triphenyltin (TPT) against multiple UDP-glucuronosyltransferases (UGT): A new potential mechanism underlying endocrine disrupting actions.  FOOD AND CHEMICAL TOXICOLOGY,      [PMID:33549631] [10.1016/j.fct.2021.112039]

10. Zhenzhen Ying, Jingyao Wei, Ruijuan Liu, Fang Zhao, Yifang Yu, Xin Tian.  (2020)  An UPLC-MS/MS Method for Determination of Osimertinib in Rat Plasma: Application to Investigating the Effect of Ginsenoside Rg3 on the Pharmacokinetics of Osimertinib.  International Journal of Analytical Chemistry,      [PMID:33456471] [10.1155/2020/8814214]

11. Yue-Yue Chang, Hai-Long Wu, Huan Fang, Tong Wang, Yang-Zi Ouyang, Xiao-Dong Sun, Gao-Yan Tong, Yu-Jie Ding, Ru-Qin Yu.  (2020)  Comparison of three chemometric methods for processing HPLC-DAD data with time shifts: Simultaneous determination of ten molecular targeted anti-tumor drugs in different biological samples.  TALANTA,      [PMID:33379025] [10.1016/j.talanta.2020.121798]

12. Ling Xiao, Dehui Chi, Guiju Sheng, Wenjuan Li, Penghui Lin, Sicheng Liang, Liangliang Zhu, Peipei Dong.  (2020)  Inhibitory effects of UDP-glucuronosyltransferase (UGT) typical ligands against E. coli beta-glucuronidase (GUS).  RSC Advances,  10  (39): (22966-22971).  [PMID:35520305] [10.1039/D0RA02311F]

13. Qianqian Wang, Yuwei Liu, Yuanyuan Zheng, Di Chen, Ya Xie, Nian Shi.  (2024)  MonoTip C18 pipette tip solid-phase extraction coupled with liquid chromatography-tandem mass spectrometry enables rapid and automated therapeutic drug monitoring of tyrosine kinase inhibitors.  Arabian Journal of Chemistry,      [PMID:] [10.1016/j.arabjc.2024.105976]

14. Zepeng Su, Yipeng Zeng, Qibo Li, Jinteng Li, Guan Zheng, Weihao Zhang, Zipeng Xiao, Zibin Chen, Yangfeng Lin, Ziqian Liu, Yanfeng Wu, Jiajie Lin, Wenhui Yu, Zhongyu Xie.  (2026)  Pim1 Serves as a Therapeutic Target for Inflammatory Arthritis via Mitochondrial Metabolism and Th17 Cell Differentiation.  Research,      [PMID:41767599] [10.34133/research.1137]