Voxelotor (GBT440) - Moligand™, ≥98% , Hemoglobin HbA positive modulator, CAS No.1446321-46-5, Hemoglobin HbA positive modulator

CAS: 1446321-46-5 Cat. No.: V414047 Molecular Weight: 337.37 EC Number: 879-126-0 PubChem CID: 71602803

GRADE & PURITY Moligand™, ≥98%

Synonyms

2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)-3-pyridinyl)methoxy)benzaldehyde | 3ZO554A4Q8 | Voxelotor [USAN] | AKOS030526545 | VOXELOTOR [WHO-DD] | GTX011 | GTX-011 | NCGC00095683-02 | 2-HYDROXY-6-((2-(1-ISOPROPYL-1H-PYRAZOL-5-YL)PYRIDIN-3-YL)METHOXY) B

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Overview

Information

Voxelotor (GBT440, GTx011) is a novel small moleculehemoglobin modifierwhich increases hemoglobin oxygen affinity.

In vitro

GBT440 is a new potent allosteric effector of sickle cell hemoglobin that increases the affinity of hemoglobin for oxygen and consequently inhibits its polymerization when subjected to hypoxic conditions. GBT440 inhibits these isozymes(CYP 1A2, 2C8, 2C9, 2C19, 2D6, and 3A4) with IC50 ranging from 7.9 to 148 μM. It is not a substrate for either P-gp or BCRP transporters It binds to the N-terminal a chain of Hb

In vivo

GBT440 has favorable oral bioavailability of 60, 37, and 36% in rats, dogs, and monkeys, respectively, with similar blood and plasma half-lives of approximately 20 h each. T1/2 value of GBT440 in all animal species is significantly shorter than the T1/2 of red blood cells (∼20 days), which supports that binding of GBT440 to hemoglobin is a reversible process. GBT440 is currently in Phase 3 clinical trials (NCT03036813) in SCD patients GBT440 increases haemoglobin oxygen affinity, reduces sickling and prolongs RBC half-life in a murine model of sickle cell disease. In a murine model of SCD, GBT440 extends the half-life of RBCs, reduces reticulocyte counts and prevents ex vivo RBC sickling. Importantly, oral dosing of GBT440 in animals demonstrates suitability for once daily dosing in humans and a highly selective partitioning into RBCs, which is a key therapeutic safety attribute. GBT440 shows dose proportional PK, a terminal half-life of 1.5-3 d.

Cell Research(from reference)

Concentrations：0, 300, 600, 1000 μM 

Specifications

Synonyms

2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)-3-pyridinyl)methoxy)benzaldehyde | 3ZO554A4Q8 | Voxelotor [USAN] | AKOS030526545 | VOXELOTOR [WHO-DD] | GTX011 | GTX-011 | NCGC00095683-02 | 2-HYDROXY-6-((2-(1-ISOPROPYL-1H-PYRAZOL-5-YL)PYRIDIN-3-YL)METHOXY) B

Specifications & Purity

Moligand™, ≥98%

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

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

Grade

Moligand™

Action Type

INHIBITOR, POSITIVE MODULATOR

Mechanism of action

Hemoglobin HbA positive modulator

Purity

≥98%

Product Properties

• ALogP: 2.7

Names and Identifiers

• Pubchem Sid: 504772179
• Pubchem Sid Url: https://pubchem.ncbi.nlm.nih.gov/substance/504772179
• Canonical Smiles: CC(C)N1C(=CC=N1)C2=C(C=CC=N2)COC3=CC=CC(=C3C=O)O
• IUPAC Name: 2-hydroxy-6-[[2-(2-propan-2-ylpyrazol-3-yl)pyridin-3-yl]methoxy]benzaldehyde
• InChIKey: FWCVZAQENIZVMY-UHFFFAOYSA-N
• INCHI: 1S/C19H19N3O3/c1-13(2)22-16(8-10-21-22)19-14(5-4-9-20-19)12-25-18-7-3-6-17(24)15(18)11-23/h3-11,13,24H,12H2,1-2H3
• Isomeric SMILES: CC(C)N1C(=CC=N1)C2=C(C=CC=N2)COC3=CC=CC(=C3C=O)O
• PubChem CID: 71602803
• Molecular Weight: 337.37

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organic oxygen compounds
    • Class Organooxygen compounds
      • Subclass Carbonyl compounds
        • Level5 Aldehydes
          • Level6 Aryl-aldehydes
            • Level7 Benzaldehydes
              • Level8 Hydroxybenzaldehydes

• Kingdom: Organic compounds
• Superclass: Organic oxygen compounds
• Class: Organooxygen compounds
• Subclass: Carbonyl compounds
• Intermediate Tree Nodes: Aldehydes - Aryl-aldehydes - Benzaldehydes
• Direct Parent: Hydroxybenzaldehydes
• Alternative Parents: Phenoxy compounds Phenol ethers Benzoyl derivatives Alkyl aryl ethers 1-hydroxy-4-unsubstituted benzenoids 1-hydroxy-2-unsubstituted benzenoids Pyridines and derivatives Vinylogous acids Pyrazoles Heteroaromatic compounds Azacyclic compounds Organonitrogen compounds Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: Hydroxybenzaldehyde - Phenoxy compound - Benzoyl - Phenol ether - Alkyl aryl ether - 1-hydroxy-4-unsubstituted benzenoid - 1-hydroxy-2-unsubstituted benzenoid - Phenol - Monocyclic benzene moiety - Pyridine - Benzenoid - Azole - Heteroaromatic compound - Pyrazole - Vinylogous acid - Ether - Azacycle - Organoheterocyclic compound - Organonitrogen compound - Hydrocarbon derivative - Organic nitrogen compound - Organic oxide - Aromatic heteromonocyclic compound
• Description: This compound belongs to the class of organic compounds known as hydroxybenzaldehydes. These are organic aromatic compounds containing a benzene ring carrying an aldehyde group and a hydroxyl group.
• 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)

CYP2C8 Tchem Cytochrome P450 2C8 (0 Activities)

Discover Target: CYP2C8

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

CYP3A4 Tclin Cytochrome P450 3A4 (0 Activities)

Discover Target: CYP3A4

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

CYP2C9 Tchem Cytochrome P450 2C9 (0 Activities)

Discover Target: CYP2C9

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

CYP2C8 Tchem Cytochrome P450 2C8 (1492 Activities)

Discover Target: CYP2C8

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

CYP2D6 Tclin Cytochrome P450 2D6 (33882 Activities)

Discover Target: CYP2D6

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

CYP1A2 Tchem Cytochrome P450 1A2 (26471 Activities)

Discover Target: CYP1A2

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

CYP2C9 Tchem Cytochrome P450 2C9 (32119 Activities)

Discover Target: CYP2C9

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

CYP2C19 Tchem Cytochrome P450 2C19 (29246 Activities)

Discover Target: CYP2C19

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

CYP3A4 Tclin Cytochrome P450 3A4 (53859 Activities)

Discover Target: CYP3A4

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

HBA1 Tclin Hemoglobin HbA (880 Activities)

Discover Target: HBA1

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

Associated Targets(non-human)

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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Rattus norvegicus (775804 Activities)

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Rhesus monkey (3147 Activities)

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rep Replicase polyprotein 1ab (378 Activities)

Discover Target: rep

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

Blood (6 Activities)

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Plasma (328 Activities)

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Mechanisms of Action

Chemical and Physical Properties

• Solubility: DMSO : ≥ 125 mg/mL (370.51 mM)
• Molecular Weight: 337.400 g/mol
• XLogP3: 2.700
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 6
• Exact Mass: 337.143 Da
• Monoisotopic Mass: 337.143 Da
• Topological Polar Surface Area: 77.200 Ų
• Heavy Atom Count: 25
• Formal Charge: 0
• Complexity: 434.000
• 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