PHA-680632 | CAS#398493-79-3 | Aurora kinase inhibitor

PHA-680632
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WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 406160

CAS#: 398493-79-3

Description: PHA-680632 is a is potent inhibitor of Aurora A, Aurora B and Aurora C with IC50 of 27 nM, 135 nM and 120 nM, respectively. PHA-680632 is also the first representative of a new class of Aurora inhibitors with a high potential for further development as an anticancer therapeutic. PHA-680632 is active on a wide range of cancer cell lines and shows significant tumor growth inhibition in different animal tumor models at well-tolerated doses.

Chemical Structure

PHA-680632

CAS# 398493-79-3

Product data Instruction

Theoretical Analysis

MedKoo Cat#: 406160
Name: PHA-680632
CAS#: 398493-79-3
Chemical Formula: C28H35N7O2
Exact Mass: 501.29
Molecular Weight: 501.635
Elemental Analysis: C, 67.04; H, 7.03; N, 19.55; O, 6.38

Price and Availability

Size	Price	Availability
5mg	USD 350	2 Weeks
10mg	USD 600	2 Weeks
25mg	USD 1100	2 Weeks
Bulk inquiry Welcome, Customer: Please do not inquire quote if your intended use is for a patient since our products are for research use and for chemical synthesis use, not for human use . For in-stock products, we listed price in the web page. You may inquire prices for which sizes were not listed. If no price is listed, this means the product is not in stock at the moment, which may be available via custom synthesis. For cost-effective reason, minimum order of 1g is requested (typically very expensive). The lead time is usually 2-4 months. Quote of less than 1g will not be provided. MedKoo may not offer quote for below reasons: (1) current available synthetic method appears to be extremely expensive which is obviously not affordable to most customers; (2) Key raw material to make the product is temporally not available; (3) DEA controlled substances; (4) the product is under patent protection in customer’s country.

Synonym: PHA680632; PHA 680632; PHA-680632.

IUPAC/Chemical Name: N-(2,6-diethylphenyl)-3-(4-(4-methylpiperazin-1-yl)benzamido)pyrrolo[3,4-c]pyrazole-5(1H,4H,6H)-carboxamide

InChi Key: OBWNXGOQPLDDPS-UHFFFAOYSA-N

InChi Code: InChI=1S/C28H35N7O2/c1-4-19-7-6-8-20(5-2)25(19)29-28(37)35-17-23-24(18-35)31-32-26(23)30-27(36)21-9-11-22(12-10-21)34-15-13-33(3)14-16-34/h6-12H,4-5,13-18H2,1-3H3,(H,29,37)(H2,30,31,32,36)

SMILES Code: O=C(N(C1)CC2=C1C(NC(C3=CC=C(N4CCN(C)CC4)C=C3)=O)=NN2)NC5=C(CC)C=CC=C5CC

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

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

More Info:

Product Data:

Product Data

Instruction:

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Biological target:	PHA-680632 is an aurora kinase inhibitor with IC50s of 27, 135 and 120 nM for aurora A, B and C.
In vitro activity:	In further clonogenic assay, PHA680632 (24 h exposure) proved to be an effective inhibitor of colony formation in vitro, with a dose-dependent effect at the range of 50 nm to 2.5 μm in different cell lines. Clonogenic survival of HCT116, HT29, and A549 cells exposed to a concentration range of PHA680632 are shown in Figure 2. PHA680632 could inhibit the colony formation even with a concentration of 50–100 nm in HCT116 cell lines, while 1 μm of PHA680632 induced only a slight clonogenic survival reduction in HT29 cells. Reference: Br J Cancer. 2007 Dec 17;97(12):1664-72. https://pubmed.ncbi.nlm.nih.gov/18026198/
In vivo activity:	PHA-680632 is active on a wide range of cancer cell lines and shows significant tumor growth inhibition in different animal tumor models at well-tolerated doses. The mechanism of action of PHA-680632 is in agreement with inhibition of Aurora kinases. Histone H3 phosphorylation in Ser10 is mediated by Aurora B kinase, and our kinetic studies on its inhibition by PHA-680632 in vitro and in vivo show that phosphorylation of histone H3 is a good biomarker to follow activity of PHA-680632. Reference: Clin Cancer Res. 2006 Jul 1;12(13):4080-9. https://pubmed.ncbi.nlm.nih.gov/16818708/

Solubility Data

	Solvent	Max Conc. mg/mL	Max Conc. mM
Solubility
	DMF	30.0	59.80
	DMSO	53.3	106.32
	DMSO:PBS (pH 7.2) (1:2)	0.3	65.78

Preparing Stock Solutions

The following data is based on the product molecular weight 501.64 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:	1. Tao Y, Zhang P, Frascogna V, Lecluse Y, Auperin A, Bourhis J, Deutsch E. Enhancement of radiation response by inhibition of Aurora-A kinase using siRNA or a selective Aurora kinase inhibitor PHA680632 in p53-deficient cancer cells. Br J Cancer. 2007 Dec 17;97(12):1664-72. doi: 10.1038/sj.bjc.6604083. Epub 2007 Nov 20. PMID: 18026198; PMCID: PMC2360282. 2. Soncini C, Carpinelli P, Gianellini L, Fancelli D, Vianello P, Rusconi L, Storici P, Zugnoni P, Pesenti E, Croci V, Ceruti R, Giorgini ML, Cappella P, Ballinari D, Sola F, Varasi M, Bravo R, Moll J. PHA-680632, a novel Aurora kinase inhibitor with potent antitumoral activity. Clin Cancer Res. 2006 Jul 1;12(13):4080-9. doi: 10.1158/1078-0432.CCR-05-1964. PMID: 16818708.
In vitro protocol:	1. Tao Y, Zhang P, Frascogna V, Lecluse Y, Auperin A, Bourhis J, Deutsch E. Enhancement of radiation response by inhibition of Aurora-A kinase using siRNA or a selective Aurora kinase inhibitor PHA680632 in p53-deficient cancer cells. Br J Cancer. 2007 Dec 17;97(12):1664-72. doi: 10.1038/sj.bjc.6604083. Epub 2007 Nov 20. PMID: 18026198; PMCID: PMC2360282. 2. Soncini C, Carpinelli P, Gianellini L, Fancelli D, Vianello P, Rusconi L, Storici P, Zugnoni P, Pesenti E, Croci V, Ceruti R, Giorgini ML, Cappella P, Ballinari D, Sola F, Varasi M, Bravo R, Moll J. PHA-680632, a novel Aurora kinase inhibitor with potent antitumoral activity. Clin Cancer Res. 2006 Jul 1;12(13):4080-9. doi: 10.1158/1078-0432.CCR-05-1964. PMID: 16818708.
In vivo protocol:	1. Tao Y, Zhang P, Frascogna V, Lecluse Y, Auperin A, Bourhis J, Deutsch E. Enhancement of radiation response by inhibition of Aurora-A kinase using siRNA or a selective Aurora kinase inhibitor PHA680632 in p53-deficient cancer cells. Br J Cancer. 2007 Dec 17;97(12):1664-72. doi: 10.1038/sj.bjc.6604083. Epub 2007 Nov 20. PMID: 18026198; PMCID: PMC2360282. 2. Soncini C, Carpinelli P, Gianellini L, Fancelli D, Vianello P, Rusconi L, Storici P, Zugnoni P, Pesenti E, Croci V, Ceruti R, Giorgini ML, Cappella P, Ballinari D, Sola F, Varasi M, Bravo R, Moll J. PHA-680632, a novel Aurora kinase inhibitor with potent antitumoral activity. Clin Cancer Res. 2006 Jul 1;12(13):4080-9. doi: 10.1158/1078-0432.CCR-05-1964. PMID: 16818708.

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1: Polacchini A, Albani C, Baj G, Colliva A, Carpinelli P, Tongiorgi E. Combined cisplatin and aurora inhibitor treatment increase neuroblastoma cell death but surviving cells overproduce BDNF. Biol Open. 2016 Jun 2. pii: bio.016725. doi: 10.1242/bio.016725. [Epub ahead of print] PubMed PMID: 27256407.

2: Mazzera L, Lombardi G, Abeltino M, Ricca M, Donofrio G, Giuliani N, Cantoni AM, Corradi A, Bonati A, Lunghi P. Aurora and IKK kinases cooperatively interact to protect multiple myeloma cells from Apo2L/TRAIL. Blood. 2013 Oct 10;122(15):2641-53. doi: 10.1182/blood-2013-02-482356. Epub 2013 Aug 23. PubMed PMID: 23974204.

3: Ratushny V, Pathak HB, Beeharry N, Tikhmyanova N, Xiao F, Li T, Litwin S, Connolly DC, Yen TJ, Weiner LM, Godwin AK, Golemis EA. Dual inhibition of SRC and Aurora kinases induces postmitotic attachment defects and cell death. Oncogene. 2012 Mar 8;31(10):1217-27. doi: 10.1038/onc.2011.314. Epub 2011 Jul 25. PubMed PMID: 21785464; PubMed Central PMCID: PMC3204164.

4: Tao Y, Zhang P, Frascogna V, Lecluse Y, Auperin A, Bourhis J, Deutsch E. Enhancement of radiation response by inhibition of Aurora-A kinase using siRNA or a selective Aurora kinase inhibitor PHA680632 in p53-deficient cancer cells. Br J Cancer. 2007 Dec 17;97(12):1664-72. Epub 2007 Nov 20. PubMed PMID: 18026198; PubMed Central PMCID: PMC2360282.

5: Soncini C, Carpinelli P, Gianellini L, Fancelli D, Vianello P, Rusconi L, Storici P, Zugnoni P, Pesenti E, Croci V, Ceruti R, Giorgini ML, Cappella P, Ballinari D, Sola F, Varasi M, Bravo R, Moll J. PHA-680632, a novel Aurora kinase inhibitor with potent antitumoral activity. Clin Cancer Res. 2006 Jul 1;12(13):4080-9. PubMed PMID: 16818708.

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