Rucaparib phosphate
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MedKoo CAT#: 200124

CAS#: 459868-92-9 (phosphate)

Description: Rucaparib, also known as AG-14699 or PF-01367338, is a tricyclic indole poly(ADP-Ribose) polymerase (PARP1) inhibitor with potential chemosensitizing, radiosensitizing, and antineoplastic activities. Rucaparib selectively binds to PARP1 and inhibits PARP1-mediated DNA repair, thereby enhancing the accumulation of DNA strand breaks and promoting genomic instability and apoptosis. This may enhance the cytotoxicity of DNA-damaging agents and reverse tumor cell resistance to chemotherapy and radiation therapy.


Chemical Structure

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Rucaparib phosphate
CAS# 459868-92-9 (phosphate)

Theoretical Analysis

MedKoo Cat#: 200124
Name: Rucaparib phosphate
CAS#: 459868-92-9 (phosphate)
Chemical Formula: C19H18FN3O
Exact Mass: 323.14339
Molecular Weight: 323.36
Elemental Analysis:

Price and Availability

Size Price Availability Quantity
25.0mg USD 90.0 Ready to ship
50.0mg USD 150.0 Ready to ship
100.0mg USD 250.0 Ready to ship
200.0mg USD 450.0 Ready to ship
500.0mg USD 950.0 Ready to ship
1.0g USD 1650.0 Ready to ship
2.0g USD 2950.0 Ready to ship
5.0g USD 5850.0 Ready to ship
10.0g USD 8950.0 Ready to ship
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Related CAS #: 283173-50-2 (free base)   459868-92-9 (phosphate)   1859053-21-6 (camsylate)  

Synonym: AG14699 (as phosphate salt); AG 14699; AG-14699; AG014447 (as free base); AG-014447; AG 014447; PF01367338; PF-01367338; PF 01367338; Rucaparib; Rubraca;

IUPAC/Chemical Name: 8-fluoro-2-(4-((methylamino)methyl)phenyl)-4,5-dihydro-1H-azepino[5,4,3-cd]indol-6(3H)-one phosphate

InChi Key: FCCGJTKEKXUBFZ-UHFFFAOYSA-N

InChi Code: InChI=1S/C19H18FN3O.H3O4P/c1-21-10-11-2-4-12(5-3-11)18-14-6-7-22-19(24)15-8-13(20)9-16(23-18)17(14)15;1-5(2,3)4/h2-5,8-9,21,23H,6-7,10H2,1H3,(H,22,24);(H3,1,2,3,4)

SMILES Code: O=C1NCCC2=C(C3=CC=C(CNC)C=C3)NC4=C2C1=CC(F)=C4.O=P(O)(O)O

Appearance: Light yellow 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

Biological target: Rucaparib phosphate (AG-014699 phosphate) is a PARP inhibitor, with a Ki of 1.4 nM for PARP1 in cell-free assay.
In vitro activity: The results thus far have demonstrated that rucaparib leads to prolonged accumulation of p53 and enhancement of growth arrest in response to DNA damage in immortalized non-transformed RPE1-hTERT cells. To assess whether these findings were applicable to cancer cells where rucaparib may provide clinical benefit, this study examined the single cell dynamics of p53 in response to rucaparib and NCS in the MCF-7 breast cancer cell line using long-term fluorescence microscopy (Figure 6A). These cells express wild-type p53 and retain BRCA function, avoiding potential synergistic killing from PARP inhibition. In response to 400 ng/mL NCS, additional treatment with rucaparib led to prolonged accumulation of p53 during the first pulse. Similar to RPE1-hTERT cells, this led to reduced pulses over 24 h (Figure 6B), increased amplitude (Figure 6C), increased time of first peak (Figure 6D), and an increased duration of the first pulse (Figure 6E). Reference: Cell Rep. 2020 Oct 13; 33(2): 108240. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605912/
In vivo activity: In WT mice treated with saline, 40.5 ± 7.14% of vessels were mismatched, while those treated with rucaparib had 17.1 ± 9.26% mismatched vessels (p = 0.026). Conversely, rucaparib treatment did not affect the degree of vessel mismatch in PARP-1-/- mice; vessel mismatch in saline-treated mice was 40.3 ± 18.8%, while in rucaparib-treated mice, vessel mismatch was 50.9 ± 18.9% (p = 0.53; Fig. 4A and B), indicating that the PARP inhibitor lacked potency in PARP null vessels. This observation was supported by real-time monitoring of the accumulation of BSA-647 in B16 tumors in dorsal window chambers, when treatment with rucaparib in WT mice evoked impressive accumulation of fluorescence in tumors (1.85-fold increase in fluorescence above initial baseline in WT, 0.97-fold in PARP-1-/-; p = 0.004—Fig. 4C), while levels of BSA-647 following similar treatment in PARP-1-/- mice failed to increase above baseline plateau (exemplar of one mouse from both groups can be seen in Fig. 4D). Reference: PLoS One. 2015; 10(2): e0118187. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4331495/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 46.0 142.26
DMSO:PBS (pH 7.2) (1:1) 0.5 1.55
DMF 0.5 1.55
Water 7.0 21.65

Preparing Stock Solutions

The following data is based on the product molecular weight 323.36 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.

Recalculate based on batch purity %
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. Hanson RL, Batchelor E. Rucaparib Treatment Alters p53 Oscillations in Single Cells to Enhance DNA-Double-Strand-Break-Induced Cell Cycle Arrest. Cell Rep. 2020 Oct 13;33(2):108240. doi: 10.1016/j.celrep.2020.108240. PMID: 33053351; PMCID: PMC7605912. 2. Ihnen M, zu Eulenburg C, Kolarova T, Qi JW, Manivong K, Chalukya M, Dering J, Anderson L, Ginther C, Meuter A, Winterhoff B, Jones S, Velculescu VE, Venkatesan N, Rong HM, Dandekar S, Udar N, Jänicke F, Los G, Slamon DJ, Konecny GE. Therapeutic potential of the poly(ADP-ribose) polymerase inhibitor rucaparib for the treatment of sporadic human ovarian cancer. Mol Cancer Ther. 2013 Jun;12(6):1002-15. doi: 10.1158/1535-7163.MCT-12-0813. Epub 2013 May 31. PMID: 23729402; PMCID: PMC3963026. 3. McCrudden CM, O'Rourke MG, Cherry KE, Yuen HF, O'Rourke D, Babur M, Telfer BA, Thomas HD, Keane P, Nambirajan T, Hagan C, O'Sullivan JM, Shaw C, Williams KJ, Curtin NJ, Hirst DG, Robson T. Vasoactivity of rucaparib, a PARP-1 inhibitor, is a complex process that involves myosin light chain kinase, P2 receptors, and PARP itself. PLoS One. 2015 Feb 17;10(2):e0118187. doi: 10.1371/journal.pone.0118187. PMID: 25689628; PMCID: PMC4331495. 4. Murray J, Thomas H, Berry P, Kyle S, Patterson M, Jones C, Los G, Hostomsky Z, Plummer ER, Boddy AV, Curtin NJ. Tumour cell retention of rucaparib, sustained PARP inhibition and efficacy of weekly as well as daily schedules. Br J Cancer. 2014 Apr 15;110(8):1977-84. doi: 10.1038/bjc.2014.91. Epub 2014 Feb 20. PMID: 24556618; PMCID: PMC3992512.
In vitro protocol: 1. Hanson RL, Batchelor E. Rucaparib Treatment Alters p53 Oscillations in Single Cells to Enhance DNA-Double-Strand-Break-Induced Cell Cycle Arrest. Cell Rep. 2020 Oct 13;33(2):108240. doi: 10.1016/j.celrep.2020.108240. PMID: 33053351; PMCID: PMC7605912. 2. Ihnen M, zu Eulenburg C, Kolarova T, Qi JW, Manivong K, Chalukya M, Dering J, Anderson L, Ginther C, Meuter A, Winterhoff B, Jones S, Velculescu VE, Venkatesan N, Rong HM, Dandekar S, Udar N, Jänicke F, Los G, Slamon DJ, Konecny GE. Therapeutic potential of the poly(ADP-ribose) polymerase inhibitor rucaparib for the treatment of sporadic human ovarian cancer. Mol Cancer Ther. 2013 Jun;12(6):1002-15. doi: 10.1158/1535-7163.MCT-12-0813. Epub 2013 May 31. PMID: 23729402; PMCID: PMC3963026.
In vivo protocol: 1. McCrudden CM, O'Rourke MG, Cherry KE, Yuen HF, O'Rourke D, Babur M, Telfer BA, Thomas HD, Keane P, Nambirajan T, Hagan C, O'Sullivan JM, Shaw C, Williams KJ, Curtin NJ, Hirst DG, Robson T. Vasoactivity of rucaparib, a PARP-1 inhibitor, is a complex process that involves myosin light chain kinase, P2 receptors, and PARP itself. PLoS One. 2015 Feb 17;10(2):e0118187. doi: 10.1371/journal.pone.0118187. PMID: 25689628; PMCID: PMC4331495. 2. Murray J, Thomas H, Berry P, Kyle S, Patterson M, Jones C, Los G, Hostomsky Z, Plummer ER, Boddy AV, Curtin NJ. Tumour cell retention of rucaparib, sustained PARP inhibition and efficacy of weekly as well as daily schedules. Br J Cancer. 2014 Apr 15;110(8):1977-84. doi: 10.1038/bjc.2014.91. Epub 2014 Feb 20. PMID: 24556618; PMCID: PMC3992512.

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1: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Available from http://www.ncbi.nlm.nih.gov/books/NBK548767/ PubMed PMID: 31644076.

2: Pearre DC, Tewari KS. Targeted treatment of advanced ovarian cancer: spotlight on rucaparib. Ther Clin Risk Manag. 2018 Nov 2;14:2189-2201. doi: 10.2147/TCRM.S149248. eCollection 2018. Review. PubMed PMID: 30464492; PubMed Central PMCID: PMC6223341.

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4: Dal Molin GZ, Westin SN, Coleman RL. Rucaparib in ovarian cancer: extending the use of PARP inhibitors in the recurrent disease. Future Oncol. 2018 Dec;14(30):3101-3110. doi: 10.2217/fon-2018-0215. Epub 2018 Aug 14. Review. PubMed PMID: 30105925; PubMed Central PMCID: PMC6331693.

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6: Dal Molin GZ, Omatsu K, Sood AK, Coleman RL. Rucaparib in ovarian cancer: an update on safety, efficacy and place in therapy. Ther Adv Med Oncol. 2018 Jun 22;10:1758835918778483. doi: 10.1177/1758835918778483. eCollection 2018. Review. PubMed PMID: 29977351; PubMed Central PMCID: PMC6024342.

7: Colombo I, Lheureux S, Oza AM. Rucaparib: a novel PARP inhibitor for BRCA advanced ovarian cancer. Drug Des Devel Ther. 2018 Mar 21;12:605-617. doi: 10.2147/DDDT.S130809. eCollection 2018. Review. PubMed PMID: 29606854; PubMed Central PMCID: PMC5868608.

8: Musella A, Bardhi E, Marchetti C, Vertechy L, Santangelo G, Sassu C, Tomao F, Rech F, D'Amelio R, Monti M, Palaia I, Muzii L, Benedetti Panici P. Rucaparib: An emerging parp inhibitor for treatment of recurrent ovarian cancer. Cancer Treat Rev. 2018 May;66:7-14. doi: 10.1016/j.ctrv.2018.03.004. Epub 2018 Mar 23. Review. PubMed PMID: 29605737.

9: Mariappan L, Jiang XY, Jackson J, Drew Y. Emerging treatment options for ovarian cancer: focus on rucaparib. Int J Womens Health. 2017 Dec 15;9:913-924. doi: 10.2147/IJWH.S151194. eCollection 2017. Review. PubMed PMID: 29290694; PubMed Central PMCID: PMC5735986.

10: Moore DC, Ringley JT, Patel J. Rucaparib: A Poly(ADP-Ribose) Polymerase Inhibitor for BRCA-Mutated Relapsed Ovarian Cancer. J Pharm Pract. 2019 Apr;32(2):219-224. doi: 10.1177/0897190017743131. Epub 2017 Nov 22. Review. PubMed PMID: 29166829.

11: Dockery LE, Gunderson CC, Moore KN. Rucaparib: the past, present, and future of a newly approved PARP inhibitor for ovarian cancer. Onco Targets Ther. 2017 Jun 19;10:3029-3037. doi: 10.2147/OTT.S114714. eCollection 2017. Review. PubMed PMID: 28790837; PubMed Central PMCID: PMC5488752.

12: Syed YY. Rucaparib: First Global Approval. Drugs. 2017 Apr;77(5):585-592. doi: 10.1007/s40265-017-0716-2. Review. PubMed PMID: 28247266.

13: Jenner ZB, Sood AK, Coleman RL. Evaluation of rucaparib and companion diagnostics in the PARP inhibitor landscape for recurrent ovarian cancer therapy. Future Oncol. 2016 Jun;12(12):1439-56. doi: 10.2217/fon-2016-0002. Epub 2016 Apr 18. Review. PubMed PMID: 27087632; PubMed Central PMCID: PMC4976841.



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