Bimiralisib free base
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MedKoo CAT#: 206146

CAS#: 1225037-39-7 (free base)

Description: Bimiralisib, also known as PQR309, is an orally bioavailable pan inhibitor of phosphoinositide-3-kinases (PI3K) and inhibitor of the mammalian target of rapamycin (mTOR), with potential antineoplastic activity. PI3K/mTOR kinase inhibitor PQR309 inhibits the PI3K kinase isoforms alpha, beta, gamma and delta and, to a lesser extent, mTOR kinase, which may result in tumor cell apoptosis and growth inhibition in cells overexpressing PI3K/mTOR. Activation of the PI3K/mTOR pathway promotes cell growth, survival, and resistance to both chemotherapy and radiotherapy.


Chemical Structure

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Bimiralisib free base
CAS# 1225037-39-7 (free base)

Theoretical Analysis

MedKoo Cat#: 206146
Name: Bimiralisib free base
CAS#: 1225037-39-7 (free base)
Chemical Formula: C17H20F3N7O2
Exact Mass: 411.1631
Molecular Weight: 411.3892
Elemental Analysis: C, 49.63; H, 4.90; F, 13.85; N, 23.83; O, 7.78

Price and Availability

Size Price Availability Quantity
10.0mg USD 130.0 Same day
25.0mg USD 220.0 Same day
50.0mg USD 370.0 Same day
100.0mg USD 590.0 Same day
200.0mg USD 950.0 Same day
500.0mg USD 1900.0 Same day
1.0g USD 2650.0 2 weeks
2.0g USD 3950.0 2 weeks
5.0g USD 6350.0 2 weeks
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Related CAS #: 1820902-72-4 (HCl salt)   1225037-39-7 (free base)    

Synonym: PQR309; PQR-309; PQR309; Bimiralisib free base.

IUPAC/Chemical Name: 5-(4,6-dimorpholino-1,3,5-triazin-2-yl)-4-(trifluoromethyl)pyridin-2-amine

InChi Key: ADGGYDAFIHSYFI-UHFFFAOYSA-N

InChi Code: InChI=1S/C17H20F3N7O2/c18-17(19,20)12-9-13(21)22-10-11(12)14-23-15(26-1-5-28-6-2-26)25-16(24-14)27-3-7-29-8-4-27/h9-10H,1-8H2,(H2,21,22)

SMILES Code: NC1=NC=C(C2=NC(N3CCOCC3)=NC(N4CCOCC4)=N2)C(C(F)(F)F)=C1

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

Biological target: Bimiralisib (PQR309) is a brain-penetrant, pan-class I PI3K/mTOR inhibitor with IC50s of 33 nM, 451 nM, 661 nM, 708 nM and 89 nM for PI3Kα, PI3Kδ, PI3Kβ, PI3Kγ and mTOR, respectively.
In vitro activity: The results of a CCK-8 assay revealed a significant suppressive effect of PQR309 on U87 and U251 cells. The results indicated that the viability of the cells was significantly (P<0.05) suppressed in a dose- and time-dependent manner after the cells were treated with PQR309 (0, 1, 5, 10, 50 and 100 µM) after 72 h (Fig. 1B). The colony formation rates of treated U87 and U251 cells decreased in various concentration groups compared to the control (Fig. 1C-D). According to these results, the IC50 values of PQR309 were 7.104 (95% CI, 5.6–8.5) and 11.986 (95% CI, 10.6–13.4) in U87 and U251 cells, respectively. Reference: Oncol Rep. 2020 Mar; 43(3): 773–782. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7040887/
In vivo activity: Rats were injected with 2 × 107 human PC3 prostate cancer cells into one flank and randomized after 16 days. From day 17 the control group received vehicle once daily. Compound 1 (bimiralisib) was orally administered at 5 mg/kg, 10 mg/kg (both daily, QD), or 15 mg/kg [5 consecutive days, 2 days off drug (QD × 5, 2 days off)] for 28 days to match the timelines of regulatory toxicology studies. Treatment with 1 led to significant tumor size reductions: tumor growth was inhibited dose-dependently (best T/C of 31–12%, Figure 6A). Compound 1 was best tolerated at 5 mg/kg without significant body weight changes (Figure 6B). At 10 mg/kg, 1 caused a reduction of body weight, which accumulated to a reduction of 15% after 28 days of treatment. Similarly, 15 mg/kg of 1 led to body weight loss after 5 days of treatment, which was reversible during the recovery period. After 28 days of drug exposure (day 44 of the experiment), animals with body weight loss fully recovered within a treatment-free period (days 45–50) without overt signs of tumor cell proliferation. In a subsequent treatment period tumor growth remained inhibited and body weight loss was only observed in the 15 mg/kg group. Reference: J Med Chem. 2017 Sep 14; 60(17): 7524–7538. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5656176/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 22.0 53.48
DMF 10.0 24.31
Ethanol 2.0 4.86

Preparing Stock Solutions

The following data is based on the product molecular weight 411.3892 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. Yang K, Tang XJ, Xu FF, Liu JH, Tan YQ, Gao L, Sun Q, Ding X, Liu BH, Chen QX. PI3K/mTORC1/2 inhibitor PQR309 inhibits proliferation and induces apoptosis in human glioblastoma cells. Oncol Rep. 2020 Mar;43(3):773-782. doi: 10.3892/or.2020.7472. Epub 2020 Jan 20. PMID: 32020210; PMCID: PMC7040887. 2. Tarantelli C, Gaudio E, Arribas AJ, Kwee I, Hillmann P, Rinaldi A, Cascione L, Spriano F, Bernasconi E, Guidetti F, Carrassa L, Pittau RB, Beaufils F, Ritschard R, Rageot D, Sele A, Dossena B, Rossi FM, Zucchetto A, Taborelli M, Gattei V, Rossi D, Stathis A, Stussi G, Broggini M, Wymann MP, Wicki A, Zucca E, Cmiljanovic V, Fabbro D, Bertoni F. PQR309 Is a Novel Dual PI3K/mTOR Inhibitor with Preclinical Antitumor Activity in Lymphomas as a Single Agent and in Combination Therapy. Clin Cancer Res. 2018 Jan 1;24(1):120-129. doi: 10.1158/1078-0432.CCR-17-1041. Epub 2017 Oct 24. PMID: 29066507. 3. von Achenbach C, Weller M, Kaulich K, Gramatzki D, Zacher A, Fabbro D, Reifenberger G, Szabó E. Synergistic growth inhibition mediated by dual PI3K/mTOR pathway targeting and genetic or direct pharmacological AKT inhibition in human glioblastoma models. J Neurochem. 2020 May;153(4):510-524. doi: 10.1111/jnc.14899. Epub 2020 Jan 8. PMID: 31618458. 4. Beaufils F, Cmiljanovic N, Cmiljanovic V, Bohnacker T, Melone A, Marone R, Jackson E, Zhang X, Sele A, Borsari C, Mestan J, Hebeisen P, Hillmann P, Giese B, Zvelebil M, Fabbro D, Williams RL, Rageot D, Wymann MP. 5-(4,6-Dimorpholino-1,3,5-triazin-2-yl)-4-(trifluoromethyl)pyridin-2-amine (PQR309), a Potent, Brain-Penetrant, Orally Bioavailable, Pan-Class I PI3K/mTOR Inhibitor as Clinical Candidate in Oncology. J Med Chem. 2017 Sep 14;60(17):7524-7538. doi: 10.1021/acs.jmedchem.7b00930. Epub 2017 Sep 1. PMID: 28829592; PMCID: PMC5656176.
In vitro protocol: 1. Yang K, Tang XJ, Xu FF, Liu JH, Tan YQ, Gao L, Sun Q, Ding X, Liu BH, Chen QX. PI3K/mTORC1/2 inhibitor PQR309 inhibits proliferation and induces apoptosis in human glioblastoma cells. Oncol Rep. 2020 Mar;43(3):773-782. doi: 10.3892/or.2020.7472. Epub 2020 Jan 20. PMID: 32020210; PMCID: PMC7040887. 2. Tarantelli C, Gaudio E, Arribas AJ, Kwee I, Hillmann P, Rinaldi A, Cascione L, Spriano F, Bernasconi E, Guidetti F, Carrassa L, Pittau RB, Beaufils F, Ritschard R, Rageot D, Sele A, Dossena B, Rossi FM, Zucchetto A, Taborelli M, Gattei V, Rossi D, Stathis A, Stussi G, Broggini M, Wymann MP, Wicki A, Zucca E, Cmiljanovic V, Fabbro D, Bertoni F. PQR309 Is a Novel Dual PI3K/mTOR Inhibitor with Preclinical Antitumor Activity in Lymphomas as a Single Agent and in Combination Therapy. Clin Cancer Res. 2018 Jan 1;24(1):120-129. doi: 10.1158/1078-0432.CCR-17-1041. Epub 2017 Oct 24. PMID: 29066507.
In vivo protocol: 1. von Achenbach C, Weller M, Kaulich K, Gramatzki D, Zacher A, Fabbro D, Reifenberger G, Szabó E. Synergistic growth inhibition mediated by dual PI3K/mTOR pathway targeting and genetic or direct pharmacological AKT inhibition in human glioblastoma models. J Neurochem. 2020 May;153(4):510-524. doi: 10.1111/jnc.14899. Epub 2020 Jan 8. PMID: 31618458. 2. Beaufils F, Cmiljanovic N, Cmiljanovic V, Bohnacker T, Melone A, Marone R, Jackson E, Zhang X, Sele A, Borsari C, Mestan J, Hebeisen P, Hillmann P, Giese B, Zvelebil M, Fabbro D, Williams RL, Rageot D, Wymann MP. 5-(4,6-Dimorpholino-1,3,5-triazin-2-yl)-4-(trifluoromethyl)pyridin-2-amine (PQR309), a Potent, Brain-Penetrant, Orally Bioavailable, Pan-Class I PI3K/mTOR Inhibitor as Clinical Candidate in Oncology. J Med Chem. 2017 Sep 14;60(17):7524-7538. doi: 10.1021/acs.jmedchem.7b00930. Epub 2017 Sep 1. PMID: 28829592; PMCID: PMC5656176.

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 1: Big Hopes with Small Molecules - PIQUR Therapeutics AG is aiming to Turn
Cancer into a Manageable Disease. Chimia (Aarau). 2014 Dec;68(12):891-2. doi:
10.2533/chimia.2014.891. PubMed PMID: 26508614.