Bimiralisib (PQR309) - Moligand™, 10mM in DMSO , Inhibitor of mechanistic target of rapamycin kinase;Inhibitor of phosphatidylinositol-4;5-bisphosphate 3-kinase catalytic subunit alpha;Inhibitor of phosphatidylinositol-4;5-bisphosphate 3-kinase catalytic , Inhibitor of mechanistic target of rapamycin kinase;Inhibitor of phosphatidylinositol-4;5-bisphosphate 3-kinase catalytic subunit alpha;Inhibitor of phosphatidylinositol-4;5-bisphosphate 3-kinase catalytic subunit beta;Inhibitor of phosphatidylinositol-4;

CAS: 1225037-39-7 Cat. No.: B420965 Molecular Weight: 411.38

GRADE & PURITY Moligand™, 10mM in DMSO

Synonyms

AS-49856 | GTPL8383 | UNII-6Z3QHB00LB | PQR309; Bimiralisib free base | s8738 | BCP15887 | PQR 309 | Q27088437 | 5-(4,6-Di-4-morpholinyl-1,3,5-triazin-2-yl)-4-(trifluoromethyl)-2-pyridinamine | NSC785117 | NSC-785117 | A3W | Bimiralisib [USAN:INN:WHO-DD]

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Overview

Information

Bimiralisib (PQR309) is a novel brain-penetrant dualPI3K/mTORinhibitor with in vitro and in vivo antilymphoma activity. It displays excellent selectivity versus PI3K-related lipid kinases, protein kinases and unrelated targets.

Targets

PI3Kα (Cell-free assay); PI3Kβ (Cell-free assay); mTOR (Cell-free assay); PI3Kγ (Cell-free assay); PI3Kδ (Cell-free assay) 1.5 nM(Kd); 11 nM(Kd); 12 nM(Kd); 25 nM(Kd); 25 nM(Kd)

In vitro

PQR309 shows in vitro activity with a median IC50 value of 233 nmol/L (95% CI, 174-324 nmol/L) in most of the tesed lymphoma cell lines (increasing doses, 72 hours). The arrest in proliferation is mainly due to cell cycle arrest with a block in G1 rather than to apoptosis, limited to only 2/7 cell lines. PQR309 is more active in B-cell lymphoma cell lines (DLBCL, MCL, CLL, and SMZL) than in the T-cell derived ALCL. PQR309 inhibits PI3K/mTOR signaling in lymphoma cell lines. It has in vitro and in vivo antilymphoma activity as single agent and in combination.\xa0

In vivo

PQR309 is orally available, crosses the blood−brain barrier, and displayed favorable pharmacokinetic parameters in mice, rats, and dogs. It shows little clearance when exposed to rat, dog, and human liver microsomes, with a quicker turnover of PQR309 in mouse liver microsomes, where 40% of the compound was eliminated within 30 min. In female mice, plasma concentrations of PQR309 depended on the drug administration route, resulting in half-lives of approximately 13-36 min for po administration vs 9-10 min for iv administration. PQR309 shows excellent oral bioavailability (>50%). Male Beagle dogs, exposed to PQR309 at 10 mg/kg po, showed maximal drug plasma concentrations Cmax of 583 ng/mL (approximately 1.5 μM) after 60-90 min and a half-life of >7 h, which results in drug levels of approximately 0.38 μM (150 ng/mL) after 24 h. The oral bioavailability in male Beagle dogs was estimated to be 23%. Altogether the PK studies in the three models (female CD-1 mouse, female Sprague-Dawley rats, male Beagle dog) show rapid absorption of PQR309 and good oral bioavailability. PQR309 demonstrates efficiency in inhibiting proliferation in tumor cell lines (PC3 prostate cancer cells) and a rat xenograft model (PC3 xenograft model).

Cell Research(from reference)

Cell lines：lymphoma cell lines 

Concentrations：500 nmol/L 

Incubation Time：72 h 

Specifications

Synonyms

AS-49856 | GTPL8383 | UNII-6Z3QHB00LB | PQR309; Bimiralisib free base | s8738 | BCP15887 | PQR 309 | Q27088437 | 5-(4, 6-Di-4-morpholinyl-1, 3, 5-triazin-2-yl)-4-(trifluoromethyl)-2-pyridinamine | NSC785117 | NSC-785117 | A3W | Bimiralisib [USAN:INN:WHO-DD]

Specifications & Purity

Moligand™, 10mM in DMSO

Biochemical and Physiological Mechanisms

Bimiralisib (PQR309) is a novel brain-penetrant dual PI3K/mTOR inhibitor with in vitro and in vivo antilymphoma activity. It displays excellent selectivity versus PI3K-related lipid kinases, protein kinases and unrelated targets.

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

This product requires cold chain shipping. Ground and other economy services are not available.

Grade

Moligand™

Action Type

INHIBITOR

Mechanism of action

Inhibitor of mechanistic target of rapamycin kinase;Inhibitor of phosphatidylinositol-4;5-bisphosphate 3-kinase catalytic subunit alpha;Inhibitor of phosphatidylinositol-4;5-bisphosphate 3-kinase catalytic subunit beta;Inhibitor of phosphatidylinositol-4;

Names and Identifiers

• Canonical Smiles: C1COCCN1C2=NC(=NC(=N2)C3=CN=C(C=C3C(F)(F)F)N)N4CCOCC4
• IUPAC Name: 5-(4,6-dimorpholin-4-yl-1,3,5-triazin-2-yl)-4-(trifluoromethyl)pyridin-2-amine
• InChIKey: ADGGYDAFIHSYFI-UHFFFAOYSA-N
• 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)
• Isomeric SMILES: C1COCCN1C2=NC(=NC(=N2)C3=CN=C(C=C3C(F)(F)F)N)N4CCOCC4
• Alternate CAS: 1225037-39-7
• Molecular Weight: 411.38
• Reaxy-Rn: 20245212
• Reaxys-RN_link_address: https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=20245212&ln=

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Class Triazines
      • Subclass Aminotriazines

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Class: Triazines
• Subclass: Aminotriazines
• Intermediate Tree Nodes: Not available
• Direct Parent: 1,3,5-triazine-2,4-diamines
• Alternative Parents: Dialkylarylamines Aminopyridines and derivatives Morpholines Imidolactams 1,3,5-triazines Heteroaromatic compounds Oxacyclic compounds Dialkyl ethers Azacyclic compounds Primary amines Organofluorides Hydrocarbon derivatives Alkyl fluorides
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: 2,4-diamine-s-triazine - Dialkylarylamine - Aminopyridine - Morpholine - Oxazinane - Pyridine - 1,3,5-triazine - Imidolactam - Heteroaromatic compound - Tertiary amine - Dialkyl ether - Ether - Oxacycle - Azacycle - Organooxygen compound - Organonitrogen compound - Organofluoride - Organohalogen compound - Organic oxygen compound - Alkyl halide - Alkyl fluoride - Hydrocarbon derivative - Primary amine - Amine - Organic nitrogen compound - Aromatic heteromonocyclic compound
• Description: This compound belongs to the class of organic compounds known as 1,3,5-triazine-2,4-diamines. These are aromatic compounds containing a 1,3,5-triazine ring which is 2,4-disusbtituted wit amine groups.
• External Descriptors: Not available

Data sources

1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61.

DOI: 10.1186/s13321-016-0174-y

Associated Targets(Human)

PIK3CG Tclin Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (2 Activities)

Discover Target: PIK3CG

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

PIK3CA Tclin Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (3 Activities)

Discover Target: PIK3CA

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

PIK3CB Tchem Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (2 Activities)

Discover Target: PIK3CB

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

PIK3CD Tclin Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (2 Activities)

Discover Target: PIK3CD

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

MTOR Tclin Serine/threonine-protein kinase mTOR (2 Activities)

Discover Target: MTOR

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

PRKDC Tchem DNA-dependent protein kinase (1929 Activities)

Discover Target: PRKDC

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

PIK3CD Tclin PI3-kinase p110-delta subunit (6699 Activities)

Discover Target: PIK3CD

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

MTOR Tclin Serine/threonine-protein kinase mTOR (13850 Activities)

Discover Target: MTOR

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

PIK3CG Tclin PI3-kinase p110-gamma subunit (5411 Activities)

Discover Target: PIK3CG

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

PI4KB Tchem PI4-kinase beta subunit (1593 Activities)

Discover Target: PI4KB

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

PIK3CB Tchem PI3-kinase p110-beta subunit (4044 Activities)

Discover Target: PIK3CB

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

A2058 (690 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

OVCAR-3 (48710 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

PC-3 (62116 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

SK-OV-3 (52876 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

PIK3C2B Tchem Phosphatidylinositol-4-phosphate 3-kinase C2 domain-containing beta polypeptide (438 Activities)

Discover Target: PIK3C2B

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Liver (3974 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

PIK3C3 Tchem Phosphatidylinositol 3-kinase catalytic subunit type 3 (535 Activities)

Discover Target: PIK3C3

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

PIK3R1 Tchem PI3-kinase p110-alpha/p85-alpha (2589 Activities)

Discover Target: PIK3R1

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

MTOR Tclin mTORC1 (330 Activities)

Discover Target: MTOR

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Associated Targets(non-human)

PIK3CA PI3-kinase p110-alpha subunit (51 Activities)

Discover Target: PIK3CA

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Hdac6 Histone deacetylase 6 (222 Activities)

Discover Target: Hdac6

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Canis familiaris (36305 Activities)

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Mus musculus (284745 Activities)

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Rattus norvegicus (775804 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

rep Replicase polyprotein 1ab (378 Activities)

Discover Target: rep

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Brain (1 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Plasma (328 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

SARS-CoV-2 (38078 Activities)

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Mechanisms of Action

Chemical and Physical Properties

• Molecular Weight: 411.400 g/mol
• XLogP3: 1.300
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 12
• Rotatable Bond Count: 3
• Exact Mass: 411.163 Da
• Monoisotopic Mass: 411.163 Da
• Topological Polar Surface Area: 103.000 Ų
• Heavy Atom Count: 29
• Formal Charge: 0
• Complexity: 506.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 0
• Undefined Atom Stereocenter Count: 0
• Defined Bond Stereocenter Count: 0
• Undefined Bond Stereocenter Count: 0
• The total count of all stereochemical bonds: 0
• Covalently-Bonded Unit Count: 1