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]
Molecule Alteration	Missense mutation	p.D473H	Molecule Info
Resistant Disease	Medulloblastoma [ICD-11: 2A00.10]		Disease 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.