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MedKoo Cat#: 584815 | Name: Pralsetinib free base
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Description:

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

Pralsetinib, also known as BLU-667, is a highly potent, selective, next generation RET inhibitor with IC50 of 0.3-0.4 nM for WT RET, RET mutants V804L, V804M, M918T and CCDC6-RET fusion.. BLU-667 is a potent and selective inhibitor of RET mutations, fusions, and predicted resistant mutants. RET fusions are key drivers of multiple cancers, including lung and thyroid cancer, and our research suggests that RET also plays a key role in some colon and breast cancers. By simultaneously targeting the primary driver and predicted resistant mutants that render cancer cells insensitive to treatment with currently approved drugs,

Chemical Structure

Pralsetinib free base
Pralsetinib free base
CAS#2097132-94-8 (free base)

Theoretical Analysis

MedKoo Cat#: 584815

Name: Pralsetinib free base

CAS#: 2097132-94-8 (free base)

Chemical Formula: C27H32FN9O2

Exact Mass: 533.2663

Molecular Weight: 533.61

Elemental Analysis: C, 60.77; H, 6.04; F, 3.56; N, 23.62; O, 6.00

Price and Availability

Size Price Availability Quantity
5mg USD 385.00 2 Weeks
100mg USD 1,350.00 2 Weeks
200mg USD 2,250.00 2 Weeks
500mg USD 3,250.00 2 Weeks
1g USD 4,650.00 2 Weeks
2g USD 7,950.00 2 Weeks
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Related CAS #
2097132-94-8 (free base) 2097132-93-7 (trans-isomer) Pralsetinib HCl
Synonym
Pralsetinib; BLU-667; BLU 667; BLU667;
IUPAC/Chemical Name
cis-N-{(1S)-1-[6-(4-fluoro-1H-pyrazol-1-yl)pyridin-3-yl]ethyl}-1-methoxy-4-{4-methyl-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl}cyclohexane-1-carboxamide
InChi Key
MXSCYXULRDBMTH-RWYJCYHVSA-N
InChi Code
InChI=1S/C27H32FN9O2/c1-16-11-23(33-25(32-16)19-7-9-27(39-4,10-8-19)26(29)38)37(24-12-17(2)34-35-24)18(3)20-5-6-22(30-13-20)36-15-21(28)14-31-36/h5-6,11-15,18-19H,7-10H2,1-4H3,(H2,29,38)(H,34,35)/t18-,19-,27+/m0/s1
SMILES Code
O=C([C@@]1(OC)CC[C@@H](C2=NC(NC3=NNC(C)=C3)=CC(C)=N2)CC1)N[C@H](C4=CC=C(N5N=CC(F)=C5)N=C4)C
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
>3 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
View handling instruction
Biological target:
Pralsetinib (BLU-667) is a highly potent, selective RET inhibitor.
In vitro activity:
BLU-667 is a highly potent and selective RET inhibitor designed to overcome these limitations. In vitro, BLU-667 demonstrated ≥10-fold increased potency over approved MKIs against oncogenic RET variants and resistance mutants. Reference: Pharmacol Res. 2021 Oct;172:105850. https://pubmed.ncbi.nlm.nih.gov/29657135/
In vivo activity:
In vivo, mAbcb1a/1b markedly and mAbcg2 slightly limited pralsetinib brain penetration (6.3-and 1.8-fold, respectively). Testis distribution showed similar results. Abcb1a/1b;Abcg2-/- mice showed 1.5-fold higher plasma exposure, 23-fold increased brain penetration, and 4-fold reduced recovery of pralsetinib in the small intestinal content. mSlco1a/1b deficiency did not affect pralsetinib oral availability or tissue exposure. Oral coadministration of the ABCB1/ABCG2 inhibitor elacridar boosted pralsetinib plasma exposure (1.3-fold) and brain penetration (19.6-fold) in wild-type mice. Additionally, pralsetinib was a modest substrate of mCYP3A, but not of hCYP3A4, which did not noticeably restrict the oral availability or tissue distribution of pralsetinib. Reference: Cancer Discov. 2018 Jul;8(7):836-849. https://pubmed.ncbi.nlm.nih.gov/34450308/
Solvent mg/mL mM comments
Solubility
DMSO 100.0 187.40
Ethanol 13.0 24.36
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 533.61 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. Wang Y, Sparidans RW, Potters S, Lebre MC, Beijnen JH, Schinkel AH. ABCB1 and ABCG2, but not CYP3A4 limit oral availability and brain accumulation of the RET inhibitor pralsetinib. Pharmacol Res. 2021 Oct;172:105850. doi: 10.1016/j.phrs.2021.105850. Epub 2021 Aug 25. PMID: 34450308. 2. Subbiah V, Gainor JF, Rahal R, Brubaker JD, Kim JL, Maynard M, Hu W, Cao Q, Sheets MP, Wilson D, Wilson KJ, DiPietro L, Fleming P, Palmer M, Hu MI, Wirth L, Brose MS, Ou SI, Taylor M, Garralda E, Miller S, Wolf B, Lengauer C, Guzi T, Evans EK. Precision Targeted Therapy with BLU-667 for RET-Driven Cancers. Cancer Discov. 2018 Jul;8(7):836-849. doi: 10.1158/2159-8290.CD-18-0338. Epub 2018 Apr 15. PMID: 29657135.
In vitro protocol:
1. Wang Y, Sparidans RW, Potters S, Lebre MC, Beijnen JH, Schinkel AH. ABCB1 and ABCG2, but not CYP3A4 limit oral availability and brain accumulation of the RET inhibitor pralsetinib. Pharmacol Res. 2021 Oct;172:105850. doi: 10.1016/j.phrs.2021.105850. Epub 2021 Aug 25. PMID: 34450308. 2. Subbiah V, Gainor JF, Rahal R, Brubaker JD, Kim JL, Maynard M, Hu W, Cao Q, Sheets MP, Wilson D, Wilson KJ, DiPietro L, Fleming P, Palmer M, Hu MI, Wirth L, Brose MS, Ou SI, Taylor M, Garralda E, Miller S, Wolf B, Lengauer C, Guzi T, Evans EK. Precision Targeted Therapy with BLU-667 for RET-Driven Cancers. Cancer Discov. 2018 Jul;8(7):836-849. doi: 10.1158/2159-8290.CD-18-0338. Epub 2018 Apr 15. PMID: 29657135.
In vivo protocol:
1. Wang Y, Sparidans RW, Potters S, Lebre MC, Beijnen JH, Schinkel AH. ABCB1 and ABCG2, but not CYP3A4 limit oral availability and brain accumulation of the RET inhibitor pralsetinib. Pharmacol Res. 2021 Oct;172:105850. doi: 10.1016/j.phrs.2021.105850. Epub 2021 Aug 25. PMID: 34450308. 2. Subbiah V, Gainor JF, Rahal R, Brubaker JD, Kim JL, Maynard M, Hu W, Cao Q, Sheets MP, Wilson D, Wilson KJ, DiPietro L, Fleming P, Palmer M, Hu MI, Wirth L, Brose MS, Ou SI, Taylor M, Garralda E, Miller S, Wolf B, Lengauer C, Guzi T, Evans EK. Precision Targeted Therapy with BLU-667 for RET-Driven Cancers. Cancer Discov. 2018 Jul;8(7):836-849. doi: 10.1158/2159-8290.CD-18-0338. Epub 2018 Apr 15. PMID: 29657135.
1: Monaca F, Vita E, Lococo F, Tortora G, Bria E. Lazarus Response to Selpercatinib for Bleeding Colic Metastasis in a Patient With RET Fusion- Positive Pulmonary Sarcomatoid Carcinoma: A Case Report. Cureus. 2024 Jul 23;16(7):e65186. doi: 10.7759/cureus.65186. PMID: 39176355; PMCID: PMC11340252. 2: Poumeaud F, Jaffrelot M, Gomez-Roca C, Korakis I, Leonardi G, Joly M, Mazières J, Guimbaud R, Fares N, Alouani E. A double-edged sword: unusual multiple severe infections with pralsetinib: a case report and literature review. Front Med (Lausanne). 2024 Jul 30;11:1402902. doi: 10.3389/fmed.2024.1402902. PMID: 39139787; PMCID: PMC11319124. 3: Hou Y, Ren X, Chen Y, Wang Y. Cardiovascular toxicities of selective ret- specific tyrosine kinase inhibitors: a pharmacovigilance study based on the United States Food and Drug Administration Adverse Event Reporting System database. Expert Opin Drug Saf. 2024 Aug 19:1-9. doi: 10.1080/14740338.2024.2392003. Epub ahead of print. PMID: 39137926. 4: Kojima A, Nadai M, Murayama N, Yamazaki H, Katoh M. Effects of tyrosine kinase inhibitors used for the treatment of non-small cell lung carcinoma on cytochrome P450 2J2 activities. Xenobiotica. 2024 Aug 12:1-6. doi: 10.1080/00498254.2024.2389401. Epub ahead of print. PMID: 39105612. 5: Chang Z, Zhu T, Jiang H, Ou W, Wang S. A Locally Advanced NSCLC Patient Harboring a Rare KIF13A-RET Fusion Benefited from Pralsetinib: A Case Report. Curr Oncol. 2024 Jun 30;31(7):3808-3814. doi: 10.3390/curroncol31070281. PMID: 39057153; PMCID: PMC11275379. 6: Dolton MJ, Bowman C, Ma F, Cheeti S, Kuruvilla D, Kassir N, Chen Y, Liu J, Chiang PC. Integrating Dynamic in vitro Systems and Mechanistic Absorption Modeling: Case Study of Pralsetinib. J Pharm Sci. 2024 Jul 26:S0022-3549(24)00252-1. doi: 10.1016/j.xphs.2024.07.006. Epub ahead of print. PMID: 39002726. 7: Chen MF, Repetto M, Wilhelm C, Drilon A. RET Inhibitors in RET Fusion- Positive Lung Cancers: Past, Present, and Future. Drugs. 2024 Jul 13. doi: 10.1007/s40265-024-02040-5. Epub ahead of print. PMID: 38997570. 8: Velasquez E, Kassir N, Cheeti S, Kuruvilla D, Sane R, Dang S, Miles D, Lu J. Predicting overall survival from tumor dynamics metrics using parametric statistical and machine learning models: application to patients with RET-altered solid tumors. Front Artif Intell. 2024 Jun 11;7:1412865. doi: 10.3389/frai.2024.1412865. PMID: 38919267; PMCID: PMC11196751. 9: Lee ATM, Ou SI. LIBRETTO-431: Confirming the Superiority of Selpercatinib to Chemotherapy and the Lack of Efficacy of Immune Checkpoint Inhibitors in Advanced RET Fusion-Positive (RET+) NSCLC, Another Unique Never- Smoker Predominant Molecular Subtype of NSCLC. Lung Cancer (Auckl). 2024 May 23;15:75-80. doi: 10.2147/LCTT.S460147. PMID: 38807655; PMCID: PMC11130712. 10: Suchomel J, Agarwal P, Anders D, Hughes K, Tang Y, Sane R, Scalori A, Sharma S, Cheeti S. Impact of P-gp inhibition on systemic exposure of pralsetinib and dosing considerations. Clin Transl Sci. 2024 Jun;17(6):e13818. doi: 10.1111/cts.13818. PMID: 38807449; PMCID: PMC11133961. 11: Mehdi M, Szabo A, Shreenivas A, Thomas JP, Tsai S, Christians KK, Evans DB, Clarke CN, Hall WA, Erickson B, Ahmed G, Thapa B, McFall T, George B, Kurzrock R, Kamgar M. Chemotherapy-free treatment targeting fusions and driver mutations in KRAS wild-type pancreatic ductal adenocarcinoma, a case series. Ther Adv Med Oncol. 2024 May 19;16:17588359241253113. doi: 10.1177/17588359241253113. PMID: 38770091; PMCID: PMC11104030. 12: Acharya B, Saha D, Garcia Garcia N, Armstrong D, Jabali B, Hanafi M, Frett B, Ryan KR. Discovery of 9H-pyrimido[4,5-b]indole derivatives as dual RET/TRKA inhibitors. Bioorg Med Chem. 2024 May 15;106:117749. doi: 10.1016/j.bmc.2024.117749. Epub 2024 May 9. PMID: 38744018; PMCID: PMC11144469. 13: Yan H, Zeng L, Zhang Y. RET rearrangement as a mechanism of resistance to ALK-TKI in non-small cell lung cancer patient with EML4-ALK fusion: A case report. Heliyon. 2024 Apr 22;10(9):e29928. doi: 10.1016/j.heliyon.2024.e29928. PMID: 38698976; PMCID: PMC11064130. 14: Barsouk A, Elghawy O, Stone S, Singh A. Patient with mediastinal carcinoma of unknown primary with RET fusion achieves durable response with RET inhibition. Anticancer Drugs. 2024 Aug 1;35(7):653-657. doi: 10.1097/CAD.0000000000001618. Epub 2024 Apr 29. PMID: 38696710. 15: Jara MA. Management of Advanced Medullary Thyroid Carcinoma: Current Systemic Therapy Options. Crit Rev Oncog. 2024;29(3):83-90. doi: 10.1615/CritRevOncog.2024051588. PMID: 38683155. 16: Cheung KWK, Tang Y, Anders D, Barata T, Scalori A, Agarwal P, Sane R, Cheeti S. Exploring the Impact of Hepatic Impairment on Pralsetinib Pharmacokinetics. Pharmaceutics. 2024 Apr 20;16(4):564. doi: 10.3390/pharmaceutics16040564. PMID: 38675225; PMCID: PMC11053887. 17: Correction to: Pralsetinib in Patients with Advanced/Metastatic Rearranged During Transfection (RET)-Altered Thyroid Cancer: Updated Efficacy and Safety Data from the ARROW Study'' by Subbiah et al. Thyroid 2024;34(1):26-40; doi: 10.1089/thy.2023.0363. Thyroid. 2024 Apr 16. doi: 10.1089/thy.2023.0363.correx. Epub ahead of print. Erratum for: Thyroid. 2024 Jan;34(1):26-40. doi: 10.1089/thy.2023.0363. PMID: 38625021. 18: Zhao Z, Pu Q, Sun T, Huang Q, Tong L, Fan T, Kang J, Chen Y, Zhang Y. Determination of Pralsetinib in Human Plasma and Cerebrospinal Fluid for Therapeutic Drug Monitoring by Ultra-performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS). Anticancer Agents Med Chem. 2024;24(11):867-877. doi: 10.2174/0118715206290110240326071909. PMID: 38584556. 19: Nishikawa G, Klein MA. Targeting RET alterations in non-small cell lung cancer. Curr Probl Cancer. 2024 Apr;49:101074. doi: 10.1016/j.currproblcancer.2024.101074. Epub 2024 Mar 16. PMID: 38494387. 20: Bowman C, Dolton M, Ma F, Cheeti S, Kuruvilla D, Sane R, Kassir N, Chen Y. Understanding CYP3A4 and P-gp mediated drug-drug interactions through PBPK modeling - Case example of pralsetinib. CPT Pharmacometrics Syst Pharmacol. 2024 Apr;13(4):660-672. doi: 10.1002/psp4.13114. Epub 2024 Mar 13. PMID: 38481038; PMCID: PMC11015073.