MI-463 - 10mM in DMSO , CAS No.1628317-18-9

CAS: 1628317-18-9 Cat. No.: M421992 Summenformel: C₂₄H₂₃F₃N₆S Molekulargewicht: 484.54

GRADE & PURITY 10mM in DMSO

Synonyms

1H-​Indole-​2-​carbonitrile,4-​methyl-​5-​[[4-​[[6-​(2,​2,​2-​trifluoroethyl)​thieno[2,​3-​d]​pyrimidin-​4-​yl]​amino]​-​1-​piperidinyl]​methyl]​-

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Übersicht

Information

MI-463 MI-463 is a potent inhibitor of Menin-MLL interaction with an IC50 value of 15.3 nM.

Targets

Menin-MLL interaction (Cell-free assay) 15.3 nM

In vitro

MI-463 demonstrates profound on-target activity in MLL leukemia cells. MI-463 results in substantial growth inhibition, with half-maximal growth inhibitory concentration (GI50) values of 0.23 μM, measured after 7 days of treatment in MLL leukemia cells. MI-463 is effective in inducing differentiation of MLL leukemia cells. Treatment with sub-micromolar concentrations of MI-463 also leads to markedly reduced expression of Hoxa9 and Meis1, downstream targets of MLL fusion proteins substantially upregulated in MLL leukemias.

In vivo

MI-463 shows substantial survival benefit in mouse models of MLL leukemia. It has very favorable druglike properties, including metabolic stability and PK profile in mice. MI-463 achieves high levels in peripheral blood following a single intravenous or oral dose, while also showing high oral bioavailability(∼45%). In a mouse xenograft model using MV4;11 human MLL leukemia cells implanted into BALB/c nude mice, MI-463 induces strong inhibition of tumor growth with once-daily intraperitoneal (i.p.) administration. It does not impair normal hematopoiesis in vivo.

Cell Research(from reference)

Cell lines：leukemia cells 

Incubation Time：6 or 7 days 

Specifications

Synonyme

1H-​Indole-​2-​carbonitrile,4-​methyl-​5-​[[4-​[[6-​(2,​2,​2-​trifluoroethyl)​thieno[2,​3-​d]​pyrimidin-​4-​yl]​amino]​-​1-​piperidinyl]​methyl]​-

Spezifikationen & Reinheit

10mM in DMSO

Biochemische und physiologische Mechanismen

MI-463 is a potent inhibitor of Menin-MLL interaction with an IC50 value of 15.3 nM.

Storage

Store at -80°C

Verschickt in

Dry ice packs + Cold packs

Dieses Produkt erfordert Kühlkettenversand. Grundversand und andere Economy-Optionen sind nicht verfügbar.

Aktionsart

INHIBITOR

Produkteigenschaften

• ALogP: 5.372
• hba_count: 2
• HBD-Zahl: 2
• Rotationsfähige Bindung: 6

Namen und Kennungen

• Pubchem Sid: 528765461
• Kanonisches Lächeln: CC1=C(C=CC2=C1C=C(N2)C#N)CN3CCC(CC3)NC4=C5C=C(SC5=NC=N4)CC(F)(F)F
• IUPAC Name: 4-methyl-5-[[4-[[6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-yl]amino]piperidin-1-yl]methyl]-1H-indole-2-carbonitrile
• InChIKey: DZACSLYTXLZAAF-UHFFFAOYSA-N
• INCHI: 1S/C24H23F3N6S/c1-14-15(2-3-21-19(14)8-17(11-28)31-21)12-33-6-4-16(5-7-33)32-22-20-9-18(10-24(25,26)27)34-23(20)30-13-29-22/h2-3,8-9,13,16,31H,4-7,10,12H2,1H3,(H,29,30,32)
• Isomere SMILES: CC1=C(C=CC2=C1C=C(N2)C#N)CN3CCC(CC3)NC4=C5C=C(SC5=NC=N4)CC(F)(F)F
• Molekulargewicht: 484.54
• Reaxy-Rn: 27586284
• Reaxys-RN_link_address: https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=27586284&ln=

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Klasse Thienopyrimidines

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Klasse: Thienopyrimidines
• Subclass: Not available
• Intermediate Tree Nodes: Not available
• Direct Parent: Thienopyrimidines
• Alternative Parents: Indoles 2,3,5-trisubstituted thiophenes Aralkylamines Aminopyrimidines and derivatives Substituted pyrroles Piperidines Imidolactams Benzenoids Heteroaromatic compounds Trialkylamines Nitriles Azacyclic compounds Organofluorides Hydrocarbon derivatives Alkyl fluorides
• Molecular Framework: Aromatic heteropolycyclic compounds
• Substituents: Indole - Indole or derivatives - Thienopyrimidine - 2,3,5-trisubstituted thiophene - Aminopyrimidine - Aralkylamine - Piperidine - Pyrimidine - Imidolactam - Benzenoid - Substituted pyrrole - Heteroaromatic compound - Pyrrole - Thiophene - Tertiary aliphatic amine - Tertiary amine - Azacycle - Nitrile - Carbonitrile - Alkyl halide - Alkyl fluoride - Organonitrogen compound - Organofluoride - Organohalogen compound - Hydrocarbon derivative - Cyanide - Organic nitrogen compound - Amine - Aromatic heteropolycyclic compound
• Beschreibung: This compound belongs to the class of organic compounds known as thienopyrimidines. These are heterocyclic compounds containing a thiophene ring fused to a pyrimidine ring. Thiophene is 5-membered ring consisting of four carbon atoms and one sulfur atom. Pyrimidine is a 6-membered ring consisting of four carbon atoms and two nitrogen centers at the 1- and 3- ring positions.
• 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

Zugehörige Ziele (menschlich)

MEN1 Tchem Menin (2 Activities)

Discover Target: MEN1

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

MEN1 Tchem Menin (447 Activities)

Discover Target: MEN1

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

MEN1 Tchem Menin/Histone-lysine N-methyltransferase MLL (48157 Activities)

Discover Target: MEN1

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

Wirkungsmechanismen

Chemische und physikalische Eigenschaften

• DMSO (mg/ml) Maximale Löslichkeit: 96
• DMSO (mM) Maximale Löslichkeit: 198.1260577
• Wasser (mg/ml) Maximale Löslichkeit: ＜1
• Molekulargewicht: 484.500 g/mol
• XLogP3: 5.900
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 9
• Rotatable Bond Count: 5
• Exact Mass: 484.166 Da
• Monoisotopic Mass: 484.166 Da
• Topological Polar Surface Area: 109.000 Ų
• Heavy Atom Count: 34
• Formal Charge: 0
• Complexity: 751.000
• 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