Nirogacestat
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Orders received during 11/25~11/29 will be shipped in 11/30/2020 due to Thanksgiving holiday.

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

MedKoo CAT#: 525757

CAS#: 1290543-63-3

Description: Nirogacestat, also known as PF-03084014, is a potent and selective gamma secretase (GS) inhibitor with potential antitumor activity. PF-03084014 binds to GS, blocking proteolytic activation of Notch receptors. Nirogacestat enhances the Antitumor Effect of Docetaxel in Prostate Cancer. Nirogacestat enhances docetaxel-mediated tumor response and provides a rationale to explore GSIs as adjunct therapy in conjunction with docetaxel for men with CRPC (castration-resistant prostate cancer).


Price and Availability

Size Price Shipping out time Quantity
100mg USD 1250 2 Weeks
200mg USD 2150 2 Weeks
500mg USD 2950 2 Weeks
1g USD 4850 2 Weeks
2g USD 8650 2 Weeks
5g USD 16750 2 Weeks
Inquire bulk and customized quantity

Pricing updated 2020-11-25. Prices are subject to change without notice.

Nirogacestat, purity > 98%, is in stock. Current shipping out time is about 2 weeks after order is received. CoA, QC data and MSDS documents are available in one week after order is received.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 525757
Name: Nirogacestat
CAS#: 1290543-63-3
Chemical Formula: C27H41F2N5O
Exact Mass: 489.32792
Molecular Weight: 489.65581
Elemental Analysis: C, 66.23; H, 8.44; F, 7.76; N, 14.30; O, 3.27


Synonym: PF-03084014; PF03084014; PF 03084014; PF-3084014; PF3084014; PF 3084014; Nirogacestat

IUPAC/Chemical Name: (S)-2-(((S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl-1-(neopentylamino)propan-2-yl)-1H-imidazol-4-yl)pentanamide

InChi Key: VFCRKLWBYMDAED-REWPJTCUSA-N

InChi Code: InChI=1S/C27H41F2N5O/c1-7-8-23(32-20-10-9-18-11-19(28)12-22(29)21(18)13-20)25(35)33-24-14-34(17-31-24)27(5,6)16-30-15-26(2,3)4/h11-12,14,17,20,23,30,32H,7-10,13,15-16H2,1-6H3,(H,33,35)/t20-,23-/m0/s1

SMILES Code: CCC[C@H](N[C@@H]1CC2=C(C=C(F)C=C2F)CC1)C(NC3=CN(C(C)(C)CNCC(C)(C)C)C=N3)=O


Technical Data

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:
>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


Additional Information

Notch signaling pathway inhibition may follow, which may result in the induction of apoptosis in tumor cells that overexpress Notch. The integral membrane protein GS is a multi-subunit protease complex that cleaves single-pass transmembrane proteins, such as Notch receptors, at residues within their transmembrane domains. Overexpression of the Notch signaling pathway has been correlated with increased tumor cell growth and survival.


References

1: Locatelli MA, Aftimos P, Dees EC, LoRusso PM, Pegram MD, Awada A, Huang B, Cesari R, Jiang Y, Shaik MN, Kern KA, Curigliano G. Phase I study of the gamma secretase inhibitor PF-03084014 in combination with docetaxel in patients with advanced triple-negative breast cancer. Oncotarget. 2016 Nov 30. doi: 10.18632/oncotarget.13727. [Epub ahead of print] PubMed PMID: 27906684.

2: Cui D, Dai J, Keller JM, Mizokami A, Xia S, Keller ET. Notch Pathway Inhibition Using PF-03084014, a γ-Secretase Inhibitor (GSI), Enhances the Antitumor Effect of Docetaxel in Prostate Cancer. Clin Cancer Res. 2015 Oct 15;21(20):4619-29. doi: 10.1158/1078-0432.CCR-15-0242. PubMed PMID: 26202948; PubMed Central PMCID: PMC4609279.

3: Zhang CC, Yan Z, Giddabasappa A, Lappin PB, Painter CL, Zhang Q, Li G, Goodman J, Simmons B, Pascual B, Lee J, Levkoff T, Nichols T, Xie Z. Comparison of dynamic contrast-enhanced MR, ultrasound and optical imaging modalities to evaluate the antiangiogenic effect of PF-03084014 and sunitinib. Cancer Med. 2014 Jun;3(3):462-71. doi: 10.1002/cam4.215. PubMed PMID: 24573979; PubMed Central PMCID: PMC4101737.

4: Messersmith WA, Shapiro GI, Cleary JM, Jimeno A, Dasari A, Huang B, Shaik MN, Cesari R, Zheng X, Reynolds JM, English PA, McLachlan KR, Kern KA, LoRusso PM. A Phase I, dose-finding study in patients with advanced solid malignancies of the oral γ-secretase inhibitor PF-03084014. Clin Cancer Res. 2015 Jan 1;21(1):60-7. doi: 10.1158/1078-0432.CCR-14-0607. PubMed PMID: 25231399.

5: López-Guerra M, Xargay-Torrent S, Rosich L, Montraveta A, Roldán J, Matas-Céspedes A, Villamor N, Aymerich M, López-Otín C, Pérez-Galán P, Roué G, Campo E, Colomer D. The γ-secretase inhibitor PF-03084014 combined with fludarabine antagonizes migration, invasion and angiogenesis in NOTCH1-mutated CLL cells. Leukemia. 2015 Jan;29(1):96-106. doi: 10.1038/leu.2014.143. PubMed PMID: 24781018.

6: Carol H, Maris JM, Kang MH, Reynolds CP, Kolb EA, Gorlick R, Keir ST, Wu J, Kurmasheva RT, Houghton PJ, Smith MA, Lock RB, Lyalin D. Initial testing (stage 1) of the notch inhibitor PF-03084014, by the pediatric preclinical testing program. Pediatr Blood Cancer. 2014 Aug;61(8):1493-6. doi: 10.1002/pbc.25026. Erratum in: Pediatr Blood Cancer. 2014 Sep;61(9):1716. Lyalin, Dmitry [added]. PubMed PMID: 24664981; PubMed Central PMCID: PMC4225044.

7: Arcaroli JJ, Quackenbush KS, Purkey A, Powell RW, Pitts TM, Bagby S, Tan AC, Cross B, McPhillips K, Song EK, Tai WM, Winn RA, Bikkavilli K, Vanscoyk M, Eckhardt SG, Messersmith WA. Tumours with elevated levels of the Notch and Wnt pathways exhibit efficacy to PF-03084014, a γ-secretase inhibitor, in a preclinical colorectal explant model. Br J Cancer. 2013 Aug 6;109(3):667-75. doi: 10.1038/bjc.2013.361. PubMed PMID: 23868008; PubMed Central PMCID: PMC3738122.

8: Zhang CC, Yan Z, Zong Q, Fang DD, Painter C, Zhang Q, Chen E, Lira ME, John-Baptiste A, Christensen JG. Synergistic effect of the γ-secretase inhibitor PF-03084014 and docetaxel in breast cancer models. Stem Cells Transl Med. 2013 Mar;2(3):233-42. doi: 10.5966/sctm.2012-0096. PubMed PMID: 23408105; PubMed Central PMCID: PMC3659764.

9: Zhang CC, Pavlicek A, Zhang Q, Lira ME, Painter CL, Yan Z, Zheng X, Lee NV, Ozeck M, Qiu M, Zong Q, Lappin PB, Wong A, Rejto PA, Smeal T, Christensen JG. Biomarker and pharmacologic evaluation of the γ-secretase inhibitor PF-03084014 in breast cancer models. Clin Cancer Res. 2012 Sep 15;18(18):5008-19. doi: 10.1158/1078-0432.CCR-12-1379. PubMed PMID: 22806875.

10: Samon JB, Castillo-Martin M, Hadler M, Ambesi-Impiobato A, Paietta E, Racevskis J, Wiernik PH, Rowe JM, Jakubczak J, Randolph S, Cordon-Cardo C, Ferrando AA. Preclinical analysis of the γ-secretase inhibitor PF-03084014 in combination with glucocorticoids in T-cell acute lymphoblastic leukemia. Mol Cancer Ther. 2012 Jul;11(7):1565-75. doi: 10.1158/1535-7163.MCT-11-0938. PubMed PMID: 22504949; PubMed Central PMCID: PMC3392513.

11: Wei P, Walls M, Qiu M, Ding R, Denlinger RH, Wong A, Tsaparikos K, Jani JP, Hosea N, Sands M, Randolph S, Smeal T. Evaluation of selective gamma-secretase inhibitor PF-03084014 for its antitumor efficacy and gastrointestinal safety to guide optimal clinical trial design. Mol Cancer Ther. 2010 Jun;9(6):1618-28. doi: 10.1158/1535-7163.MCT-10-0034. PubMed PMID: 20530712.

12: Papayannidis C, DeAngelo DJ, Stock W, Huang B, Shaik MN, Cesari R, Zheng X, Reynolds JM, English PA, Ozeck M, Aster JC, Kuo F, Huang D, Lira PD, McLachlan KR, Kern KA, Garcia-Manero G, Martinelli G. A Phase 1 study of the novel gamma-secretase inhibitor PF-03084014 in patients with T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma. Blood Cancer J. 2015 Sep 25;5:e350. doi: 10.1038/bcj.2015.80. PubMed PMID: 26407235; PubMed Central PMCID: PMC4648526.

13: Shang H, Braggio D, Lee YJ, Al Sannaa GA, Creighton CJ, Bolshakov S, Lazar AJ, Lev D, Pollock RE. Targeting the Notch pathway: A potential therapeutic approach for desmoid tumors. Cancer. 2015 Nov 15;121(22):4088-96. doi: 10.1002/cncr.29564. PubMed PMID: 26349011; PubMed Central PMCID: PMC4635059.

14: Wang K, Zhang Q, Li D, Ching K, Zhang C, Zheng X, Ozeck M, Shi S, Li X, Wang H, Rejto P, Christensen J, Olson P. PEST domain mutations in Notch receptors comprise an oncogenic driver segment in triple-negative breast cancer sensitive to a γ-secretase inhibitor. Clin Cancer Res. 2015 Mar 15;21(6):1487-96. doi: 10.1158/1078-0432.CCR-14-1348. PubMed PMID: 25564152.

15: Yabuuchi S, Pai SG, Campbell NR, de Wilde RF, De Oliveira E, Korangath P, Streppel MM, Rasheed ZA, Hidalgo M, Maitra A, Rajeshkumar NV. Notch signaling pathway targeted therapy suppresses tumor progression and metastatic spread in pancreatic cancer. Cancer Lett. 2013 Jul 10;335(1):41-51. doi: 10.1016/j.canlet.2013.01.054. PubMed PMID: 23402814; PubMed Central PMCID: PMC3665739.

16: Arcaroli JJ, Powell RW, Varella-Garcia M, McManus M, Tan AC, Quackenbush KS, Pitts TM, Gao D, Spreafico A, Dasari A, Touban BM, Messersmith WA. ALDH+ tumor-initiating cells exhibiting gain in NOTCH1 gene copy number have enhanced regrowth sensitivity to a γ-secretase inhibitor and irinotecan in colorectal cancer. Mol Oncol. 2012 Jun;6(3):370-81. doi: 10.1016/j.molonc.2012.03.004. PubMed PMID: 22521243; PubMed Central PMCID: PMC4033713.

17: Aguirre SA, Liu L, Hosea NA, Scott W, May JR, Burns-Naas LA, Randolph S, Denlinger RH, Han B. Intermittent oral coadministration of a gamma secretase inhibitor with dexamethasone mitigates intestinal goblet cell hyperplasia in rats. Toxicol Pathol. 2014;42(2):422-34. doi: 10.1177/0192623313486315. PubMed PMID: 23651588.

18: Samore WR, Gondi CS. Brief overview of selected approaches in targeting pancreatic adenocarcinoma. Expert Opin Investig Drugs. 2014 Jun;23(6):793-807. doi: 10.1517/13543784.2014.902933. Review. PubMed PMID: 24673265.

19: Kaur G, Reinhart RA, Monks A, Evans D, Morris J, Polley E, Teicher BA. Bromodomain and hedgehog pathway targets in small cell lung cancer. Cancer Lett. 2016 Feb 28;371(2):225-39. doi: 10.1016/j.canlet.2015.12.001. PubMed PMID: 26683772; PubMed Central PMCID: PMC4738144.

20: Zhang T, Armstrong AJ. Docetaxel Resistance in Prostate Cancer: Taking It Up a Notch. Clin Cancer Res. 2015 Oct 15;21(20):4505-7. doi: 10.1158/1078-0432.CCR-15-1613. PubMed PMID: 26307134.