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1028486-01-2 (Alisertib)

1

Identification

Alisertib Alisertib
Name Alisertib
Formula C27H20ClFN4O4
MW 518.92
CAS No. 1028486-01-2
EINECS
Smiles O=C(C1=CC=C(C=C1OC)NC2=NC=C3CN=C(C4=CC(Cl)=CC=C4C3=N2)C5=C(C=CC=C5F)OC)O
Synonyms MLN 8237;MLN8237;MLN-8237; 4-((9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-benzo[c]pyrimido[4,5-e]azepin-2-yl)amino)-2-methoxybenzoic acid
InChI InChI=1S/C27H20ClFN4O4/c1-36-21-5-3-4-20(29)23(21)25-19-10-15(28)6-8-17(19)24-14(12-30-25)13-31-27(33-24)32-16-7-9-18(26(34)35)22(11-16)37-2/h3-11,13H,12H2,1-2H3,(H,34,35)(H,31,32,33)
2

Introduction

Alisertib (MLN8237) is a selective Aurora A inhibitor with IC50 of 1.2 nM; has >200-fold higher selectivity for Aurora A than Aurora B. IC50 Value: 1.2 nM (Aurora A) Target: Aurora A in vitro: MLN8237 (0.5 μM) treatment inhibits the phosphorylation of Aurora A in MM1.S and OPM1 cells, without affecting the Aurora B mediated histone H3 phosphorylation.

Background Information

A potent, selective and orally bioavailable Aurora A Kinase inhibitor ......by AOBIOUS INC
MLN82379 (Alisertib) is a second-generation, orally bioavailable, highly selective small molecule inhibitor of the serine/threonine protein kinase Aurora A kinase with potential antineoplastic activity. MLN8237 (Alisertib) binds to and inhibits Aurora A kinase, which may result in disruption of the assembly of the mitotic spindle apparatus, disruption of chromosome segregation, and inhibition of cell proliferation. ......by AbMole BioScience
MLN8237 (Alisertib) is a selective Aurora A inhibitor with IC50 of 1.2 nM in a cell-free assay. It has >200-fold higher selectivity for Aurora A than Aurora B. Phase 3.. ......by AdooQ BioScience, LLC
Description ......by Apexbio Technology LLC
MLN8237 is a second-generation, orally bioavailable, highly selective small molecule inhibitor of the serine/threonine protein kinase Aurora A kinase with potential antineoplastic activity. Aurora kinase inhibitor MLN8237 binds to and inhibits Aurora A k ......by BOC Sciences
MLN8237 is a potent and selective inhibitor of Aurora kinase A (IC₅₀ =1.2 nM). It displays >200-fold higher selectivity for Aurora kinase A over Aurora kinase B. Displays antineoplastic activity. ......by BioVision, Inc.,
Alisertib (MLN 8237) is a selective Aurora A inhibitor with IC50 of 1.2 nM, and is more selective for Aurora A than Aurora B. ......by MedChemexpress Co., Ltd.
Alisertib, also known as MLN8237, is a second-generation, orally bioavailable, highly selective small molecule inhibitor of the serine/threonine protein kinase Aurora A kinase with potential antineoplastic activity. Aurora kinase inhibitor MLN8237 binds to and inhibits Aurora A kinase, which may result in disruption of the assembly of the mitotic spindle apparatus, disruption of chromosome segregation, and inhibition of cell proliferation. ......by MedKoo Biosciences, Inc.
A potent and highly selective inhibitor of Aurora A with IC50 of 1.2 nM; has less activity against Aurora B (IC50=396.5 nM) and a 205-kinase panel; inhibits proliferation of human tumor cell lines in vitro and produces tumor growth inhibition in solid tumor xenograft models. ......by ProbeChem
Alisertib (MLN8237) is a selective Aurora A inhibitor with IC50 of 1.2 nM in a cell-free assay. It has >200-fold higher selectivity for Aurora A than Aurora B. Phase 3. ......by Selleck Chemicals LLC
Alisertib is a second-generation, orally bioavailable, highly selective small molecule inhibitor of the serine/threonine protein kinase Aurora A kinase with potential antineoplastic activity. Alisertib binds to and inhibits Aurora A kinase, which may result in disruption of the assembly of the mitotic spindle apparatus, disruption of chromosome segregation, and inhibition of cell proliferation. Aurora A kinase localizes to the spindle poles and to spindle microtubules during mitosis, and is thought to regulate spindle assembly. Aberrant expression of Aurora kinases occurs in a wide variety of cancers, including colon and breast cancers. ......by Target Molecule Corp.
3

Protocol(Only for Reference)

Cell Experiment

Cell lines TIB-48 and CRL-2396 cells
Conditions >100 nM, 48 hours
Method TIB-48 and CRL-2396 cells were treated with MLN8237 at 10 nM, 50 nM, 100 nM, 500 nM and 1.0 μ M for 48 h. MLN8237 induced apoptosis at concentrations >100 nM, suggesting that induction of apoptosis is dose-dependent. These results were confirmed by demonstrating an increased level of cleaved PARP in treated TIB-48 and CRL-2396 cells. PARP cleavage was observed even at the concentration of MLN8237 as low as 50 nM.
Source Apexbio Technology LLC

Animal Experiment

Animal Models Female C.B-17 SCID mice injected with OVCAR-5-pWZL-Luc cells
Dosage Form Oral administration, 20 or 30 mg/kg, once daily (QD) or twice daily (BID)
Applications The mice (n=16/group) were randomly divided into five treatment groups: 1) vehicle, 2) 20 mg/kg alisertib, 3) 30 mg/kg alisertib, 4) 5 mg/kg paclitaxel and 5) 20 mg/kg alisertib + 5 mg/kg paclitaxel. Tumor growth was monitored by weekly BLI and the log-transformed total flux data showed significantly decreased tumor growth rates in mice treated with alisertib (20 or 30 mg/kg) compared to vehicle-treated mice. Treatment with 20 mg/kg and 30 mg/kg alisertib resulted in 51% and 49% TGI, respectively.
Source Apexbio Technology LLC
4

Physical and Chemical Properties

Appearance:Pink to red Solid EBNumber:EB000029060

Storage condition

Store at -20°C by Apexbio Technology LLC

Solubility

Soluble in DMSO > 10 mM by Apexbio Technology LLC
DMSO ≥42mg/mL Water <1.2mg/mL Ethanol <1.2mg/mL by MedChemexpress Co., Ltd.
5

Mechanism and Indication

6

Clinical Information

Product Name Sponsor & Collaborators Indications Start Date End Date Phase
Alisertib Millennium Pharmaceuticals Inc Peripheral T-cell lymphoma 2012/6/30 2017/2/28 Phase 3 Clinical
Alisertib Ohio State University Comprehensive Cancer Center B-cell lymphoma 2013/5/31 2014/6/30 Phase 2 Clinical
Alisertib Ohio State University Comprehensive Cancer Center Non-Hodgkin lymphoma 2013/5/31 2014/6/30 Phase 2 Clinical
Alisertib Weill Medical College of Cornell University Hormone refractory prostate cancer 2013/2/28 2016/2/29 Phase 2 Clinical
Alisertib National Cancer Institute Sarcoma 2012/8/31 2014/8/31 Phase 2 Clinical
Alisertib National Cancer Institute Leiomyosarcoma 2012/8/31 2014/8/1 Phase 2 Clinical
Alisertib - Phase 3
7

Safety Data of Alisertib

8

Spectral Information

9

Suppliers List

Company Price and Availability Country/Region
AOBIOUS INC 1mg/USD21() USA
AbMole BioScience USA
Active Biopharma Corp China
AdooQ BioScience, LLC USA
Apexbio Technology LLC USA
Ark Pharm, Inc. USA
BOC Sciences
BioVision, Inc., USA
Biochempartner Co., Ltd China
CHEMSCENE, LLC 5mg/USD72();10mg/USD120() USA
Cayman Chemical Company USA
ChemieTek USA
MedChemexpress Co., Ltd. 5mg/USD72();10mg/USD120() USA
MedKoo Biosciences, Inc. USA
ProbeChem
Selleck Chemicals LLC USA
Shanghai Haoyuan Chemexpress Co., Ltd. 5mg/USD72();10mg/USD120() China
Target Molecule Corp. 2mg/USD64();5mg/USD89();10mg/USD129();50mg/USD468() USA
10

Related Products

Other Forms of 1028486-01-2

Name CAS No Formula MW

Recommended Compounds in Aurora Kinase Autophagy

Name CAS No Formula MW
TAK-632 1228591-30-7 C27H18F4N4O3S 554.52
XL228 898280-07-4 C22H31N9O 437.54
MK-8745 885325-71-3 C20H19ClFN5OS 431.9142
ENMD-2076 934353-76-1 C21H25N7 375.47
ABT-348 1227939-82-3 C25H21FN6O2S 488.54
Reversine 656820-32-5 C21H27N7O 393.49
PF-03814735 942487-16-3 C23H25F3N6O2 474.48
MK-5108 1010085-13-8 C22H21ClFN3O3S 461.94
CCT 137690 1095382-05-0 C26H31BrN8O 551.48
SCH-1473759 (hydrochloride) 1094067-13-6 C20H27ClN8OS 462.9994
SCH-1473759 1094069-99-4 C20H26N8OS 426.54
AZD1152 722543-31-9 C26H31FN7O6P 587.54
AMG 900 945595-80-2 C28H21N7OS 503.58
TAK-901 934541-31-8 C28H32N4O3S 504.64
Hesperadin 422513-13-1 C29H32N4O3S 516.65
ENMD-2076 (Tartrate) 1291074-87-7 C25H31N7O6 525.56
CCT129202 942947-93-5 C23H25ClN8OS 497.02
PHA-680632 398493-79-3 C28H35N7O2 501.62
JNJ-7706621 443797-96-4 C15H12F2N6O3S 394.36
AZD1152-HQPA 722544-51-6 C26H30FN7O3 507.56

Recommended Compounds in Same Indication

Name CAS No Formula MW
TAK-700 (R-form) 752243-39-3 C18H17N3O2 307.35
Olaparib 763113-22-0 C24H23FN4O3 434.46
CAL-101 870281-82-6 C22H18FN7O 415.42
PU-H71 873436-91-0 C18H21IN6O2S 512.37
AT9283 896466-04-9 C19H23N7O2 381.43
KX2-391 897016-82-9 C26H29N3O3 431.53
Bicalutamide 90357-06-5 C18H14F4N2O4S 430.37
Enzalutamide 915087-33-1 C21H16F4N4O2S 464.44
Cyclophosphamide 50-18-0 C7H15Cl2N2O2P 261.09
N-Hydroxy-3-(3-phenylsulfamoylphenyl)acrylamide 414864-00-9 C15H14N2O4S 318.34766
Linsitinib 867160-71-2 C26H23N5O 421.49
Fenretinide 65646-68-6 C26H33NO2 391.55
Retaspimycin 857402-23-4 C31H45N3O8 587.7
Retaspimycin (Hydrochloride) 857402-63-2 C31H46ClN3O8 624.17
Bafetinib 859212-16-1 C30H31F3N8O 576.6154
AT13387 912999-49-6 C24H31N3O3 409.52
Vismodegib 879085-55-9 C19H14Cl2N2O3S 421.3
Tasquinimod 254964-60-8 C20H17F3N2O4 406.36
Orteronel 566939-85-3 C18H17N3O2 307.35
Orteronel (racemate) 426219-18-3 C18H17N3O2 307.3465
11

Route of Synthesis

12

References

[1]. Güllü G?rgün et al A novel Aurora-A kinase inhibitor MLN8237 induces cytotoxicity and cell-cycle arrest in multiple myeloma Blood June 24, 2010 vol. 115 no. 25 5202-5213

[2]. Dominic A. Sloane? et al Drug-Resistant Aurora A Mutants for Cellular Target Validation of the Small Molecule Kinase Inhibitors MLN8054 and MLN8237 ACS Chem. Biol., 2010, 5 (6), pp 563-576

[3]. Matulonis UA, Sharma S, Ghamande S, Gordon MS, Del Prete SA, Ray-Coquard I, Kutarska E, Liu H, Fingert H, Zhou X, Danaee H, Schilder RJ.Phase II study of MLN8237 (alisertib), an investigational Aurora A kinase inhibitor, in patients with platinum-resistant or -refractory epithelial ovarian, fallopian tube, or primary peritoneal carcinoma.Gynecol Oncol. 2012 Oct;127(1):63-9. Epub 2012 Jul 5.

[4]. Manfredi MG, Ecsedy JA, Chakravarty A, Silverman L, Zhang M, Hoar KM, Stroud SG, Chen W, Shinde V, Huck JJ, Wysong DR, Janowick DA, Hyer ML, Leroy PJ, Gershman RE, Silva MD, Germanos MS, Bolen JB, Claiborne CF, Sells TB.Characterization of Alisertib (MLN8237), an investigational small-molecule inhibitor of aurora A kinase using novel in vivo pharmacodynamic assays.Clin Cancer Res. 2011 Dec 15;17(24):7614-24. Epub 2011 Oct 20.

[5]. Sehdev V, Katsha A, Ecsedy J, Zaika A, Belkhiri A, El-Rifai W.The combination of alisertib, an investigational Aurora kinase A inhibitor, and docetaxel promotes cell death and reduces tumor growth in preclinical cell models of upper gastrointestinal adenocarcinomas.Cancer. 2012 Sep 12.

Protocol Reference

[1] Qi W, Spier C, Liu X, et al. Alisertib (MLN8237) an investigational agent suppresses Aurora A and B activity, inhibits proliferation, promotes endo-reduplication and induces apoptosis in T-NHL cell lines supporting its importance in PTCL treatment. Leukemia research, 2013, 37(4): 434-439.

[2] Do T V, Xiao F, Bickel L E, et al. Aurora kinase A mediates epithelial ovarian cancer cell migration and adhesion. Oncogene, 2013, 33(5): 539-549.

......by Apexbio Technology LLC
13

More Information

Alisertib

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