WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H206146
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.
Hodoodo Cat#: H206146
Name: Bimiralisib free base
CAS#: 1225037-39-7 (free base)
Chemical Formula: C17H20F3N7O2
Exact Mass: 411.16
Molecular Weight: 411.389
Elemental Analysis: C, 49.63; H, 4.90; F, 13.85; N, 23.83; O, 7.78
Related CAS #: 1225037-39-7 (free base) 1820902-72-4 (HCl) 1820902-73-5 (HCl hydrate)
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
More Info:
| 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 |
| 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/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 22.0 | 53.48 | |
| DMF | 10.0 | 24.31 | |
| Ethanol | 2.0 | 4.86 |
The following data is based on the product molecular weight 411.39 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. 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. |
1: Wind SS, Jansen MAA, Rijsbergen M, van Esdonk MJ, Ziagkos D, Cheng WC, Niemeyer-van der Kolk T, Korsten J, Gruszka A, Schmitz-Rohmer D, Bonnel D, Legouffe R, Barré F, Bekkenk MW, de Haas ERM, Quint KD, Rolli M, Streefkerk HJ, Burggraaf J, Vermeer MH, Rissmann R. Topical Bimiralisib Shows Meaningful Cutaneous Drug Levels in Healthy Volunteers and Mycosis Fungoides Patients but No Clinical Activity in a First-in-Human, Randomized Controlled Trial. Cancers (Basel). 2022 Mar 15;14(6):1510. doi: 10.3390/cancers14061510. Erratum in: Cancers (Basel). 2023 Feb 27;15(5): PMID: 35326659; PMCID: PMC8946662.
2: Johnson FM, Janku F, Gouda MA, Tran HT, Kawedia JD, Schmitz D, Streefkerk H, Lee JJ, Andersen CR, Deng D, Rawal S, Shah PA, El-Naggar AK, Johnson JM, Frederick MJ. Inhibition of the Phosphatidylinositol-3 Kinase Pathway Using Bimiralisib in Loss-of-Function NOTCH1-Mutant Head and Neck Cancer. Oncologist. 2022 Dec 9;27(12):1004-e926. doi: 10.1093/oncolo/oyac185. PMID: 36124629; PMCID: PMC9732253.
3: Seipel K, Brügger Y, Mandhair H, Bacher U, Pabst T. Rationale for Combining the BCL2 Inhibitor Venetoclax with the PI3K Inhibitor Bimiralisib in the Treatment of IDH2- and FLT3-Mutated Acute Myeloid Leukemia. Int J Mol Sci. 2022 Oct 20;23(20):12587. doi: 10.3390/ijms232012587. PMID: 36293442; PMCID: PMC9604078.
4: Hsin IL, Shen HP, Chang HY, Ko JL, Wang PH. Suppression of PI3K/Akt/mTOR/c-Myc/mtp53 Positive Feedback Loop Induces Cell Cycle Arrest by Dual PI3K/mTOR Inhibitor PQR309 in Endometrial Cancer Cell Lines. Cells. 2021 Oct 27;10(11):2916. doi: 10.3390/cells10112916. PMID: 34831139; PMCID: PMC8616154.
5: Collins GP, Eyre TA, Schmitz-Rohmer D, Townsend W, Popat R, Giulino-Roth L, Fields PA, Krasniqi F, Soussain C, Stathis A, Andjelkovic N, Cunningham D, Mandic D, Radulovic S, Tijanic I, Horowitz NA, Kurtovic S, Schorb E, Schmidt C, Dimitrijević S, Dreyling M. A Phase II Study to Assess the Safety and Efficacy of the Dual mTORC1/2 and PI3K Inhibitor Bimiralisib (PQR309) in Relapsed, Refractory Lymphoma. Hemasphere. 2021 Oct 27;5(11):e656. doi: 10.1097/HS9.0000000000000656. PMID: 34901759; PMCID: PMC8660000.
6: Munz N, Cascione L, Parmigiani L, Tarantelli C, Rinaldi A, Cmiljanovic N, Cmiljanovic V, Giugno R, Bertoni F, Napoli S. Exon-Intron Differential Analysis Reveals the Role of Competing Endogenous RNAs in Post-Transcriptional Regulation of Translation. Noncoding RNA. 2021 Apr 16;7(2):26. doi: 10.3390/ncrna7020026. PMID: 33923420; PMCID: PMC8167571.
7: Wind SS, Jansen MAA, Rijsbergen M, van Esdonk MJ, Ziagkos D, Cheng WC, Niemeyer-van der Kolk T, Korsten J, Gruszka A, Schmitz-Rohmer D, Bonnel D, Legouffe R, Barré F, Bekkenk MW, de Haas ERM, Quint KD, Schnidar H, Rolli M, Streefkerk HJ, Burggraaf J, Vermeer MH, Rissmann R. Correction: Wind et al. Topical Bimiralisib Shows Meaningful Cutaneous Drug Levels in Healthy Volunteers and Mycosis Fungoides Patients but No Clinical Activity in a First-in-Human, Randomized Controlled Trial. Cancers 2022, 14, 1510. Cancers (Basel). 2023 Feb 27;15(5):1485. doi: 10.3390/cancers15051485. Erratum for: Cancers (Basel). 2022 Mar 15;14(6): PMID: 36900424; PMCID: PMC10001047.
8: 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.
9: 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.
10: Choo F, Odintsov I, Nusser K, Nicholson KS, Davis L, Corless CL, Stork L, Somwar R, Ladanyi M, Davis JL, Davare MA. Functional impact and targetability of PI3KCA, GNAS, and PTEN mutations in a spindle cell rhabdomyosarcoma with MYOD1 L122R mutation. Cold Spring Harb Mol Case Stud. 2022 Jan 10;8(1):a006140. doi: 10.1101/mcs.a006140. Erratum in: Cold Spring Harb Mol Case Stud. 2022 Apr 28;8(3): PMID: 35012940; PMCID: PMC8744497.
