Drug Information

Drug (ID: DG00359) and It's Reported Resistant Information

Name	GDP-beta-L-galactose
Synonyms	GDP-beta-L-galactose; Guanosine-5'-Diphosphate-Beta-L-Galactose; guanosine 5'-diphospho-beta-L-galactopyranoside; guanosine 5'-[3-(beta-L-galactopyranosyl) dihydrogen diphosphate]; [(2R,3S,4R,5R)-5-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl (2R,3S,4R,5S,6S)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl dihydrogen diphosphate (non-preferred name); GDC; CHEBI:42660; C02280; Q27120477 Click to Show/Hide
Structure
Drug Resistance Disease(s)	Disease(s) with Clinically Reported Resistance for This Drug (1 diseases) Brain cancer [ICD-11: 2A00] [1]
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Formula	C16H25N5O16P2
IsoSMILES	C1=NC2=C(N1[C@H]3[C@@H]([C@@H]([C@H](O3)COP(=O)(O)OP(=O)(O)O[C@@H]4[C@H]([C@@H]([C@@H]([C@@H](O4)CO)O)O)O)O)O)N=C(NC2=O)N
InChI	1S/C16H25N5O16P2/c17-16-19-12-6(13(28)20-16)18-3-21(12)14-10(26)8(24)5(34-14)2-33-38(29,30)37-39(31,32)36-15-11(27)9(25)7(23)4(1-22)35-15/h3-5,7-11,14-15,22-27H,1-2H2,(H,29,30)(H,31,32)(H3,17,19,20,28)/t4-,5+,7+,8+,9+,10+,11-,14+,15+/m0/s1
InChIKey	MVMSCBBUIHUTGJ-JGQUBWHWSA-N
PubChem CID	135398680

Type(s) of Resistant Mechanism of This Drug

UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

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Brain cancer [ICD-11: 2A00]

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)		Click to Show/Hide
Key Molecule: Smoothened homolog (SMO)			[1]
Resistant Disease	Medulloblastoma [ICD-11: 2A00.10]		Disease Info
Molecule Alteration	Missense mutation	p.D473H	Molecule Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Hedgehog signaling pathway	Activation	hsa04340
Experiment for Molecule Alteration	Deep sequencing assay
Experiment for Drug Resistance	Fluorescence-activated cell sorting (FACS) analysis
Mechanism Description	Molecular profiling of the medulloblastoma patient's primary and metastatic tumor taken before treatment with GDC-0449 revealed an underlying somatic mutation in PTCH1 (PTCH1-W844C) as well as up-regulated expression of Hh pathway target genes, supporting the hypothesis that the tumor was driven by dysregulated Hh signaling. SMO-D473H transfection induced Hh pathway activity to levels comparable with that seen with SMO-WT, demonstrating that SMO-D473H is fully capable of activating Hh signaling.

References

Ref 1	Smoothened mutation confers resistance to a Hedgehog pathway inhibitor in medulloblastoma. Science. 2009 Oct 23;326(5952):572-4. doi: 10.1126/science.1179386. Epub 2009 Sep 2.