Dabrafenib-d9 is intended for use as an internal standard for the quantification of dabrafenib (Item No. 16989) by GC- or LC-MS. Dabrafenib is an ATP-competitive inhibitor of Raf kinases (IC50s = 0.64, 0.68 and 5 nM for wild-type B-RAF kinase, mutant B-RAFV600E, and wild-type C-RAF kinase, respectively).{42963} It also inhibits the tyrosine kinase-like kinases ALK5 and LIMK1 (IC50s = 11 and 15 nM, respectively) and the calcium/calmodulin-dependent protein kinases SIK2 and PDK2 (IC50s = 27 and 57 nM, respectively), as well as NEK11, CK1, and BRK (IC50s = 20, 41, and 79 nM, respectively) in a panel of 270 kinases at 300 nM. Dabrafenib inhibits the growth of 16 cancer cell lines expressing mutant B-RAFV600E (GI50s = 50s = 50s = V600E, 133 cell lines expressing wild-type Ras and Raf, or 18 cell lines expressing mutant Ras (GI50s = >10 µM) in a panel of 195 cancer cell lines. Dabrafenib (8 nM) inhibits MAPK signaling, inhibiting phosphorylation of MEK and ERK, and activates caspase-3/7 in B-RAFV600E-expressing A375P melanoma cells but not in wild-type B-RAF-expressing human foreskin fibroblasts (EC200s =71 and >10,000 nM, respectively). It reduces tumor growth in an A375P mouse xenograft model when administered at doses ranging from 3 to 100 mg/kg. Formulations containing dabrafenib have been used in the treatment of B-RAFV600E-expressing cancers.
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An internal standard for the quantification of dabrafenib by GC- or LC-MS
Formal name: N-[3-[5-(2-amino-4-pyrimidinyl)-2-[1,1-di(methyl-d3)ethyl-2,2,2-d3]-4-thiazolyl]-2-fluorophenyl]-2,6-difluoro-benzenesulfonamide
Synonyms:
Molecular weight: 528.6
CAS: 1423119-98-5
Purity: ≥99% deuterated forms (d1-d9)
Formulation: A solid
The nuclear factor-κB (NF-κB) regulates the expression of numerous genes involved in immunity and inflammation, cellular stress responses, growth, and apoptosis. Resveratrol, a polyphenolic trans-stilbene, is a known inhibitor of the activation of NF-κB and exhibits activity against a wide variety of cancer cells. CAY10512 is a substituted trans-stilbene analog of resveratrol that is 100-fold more potent as measured by antioxidant activity. The IC50 value for inhibition of TNFα-induced activation of NF-κB by CAY10512 is 0.15 µM compared to 20 µM by resveratrol.{14545}
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1,2-Dipalmitoyl-sn-glycero-3-PC (DPPC) is a zwitterionic glycerophospholipid commonly used in the formation of lipid monolayers, bilayers, and liposomes for use in a variety of applications.{14480,24261,14478,14479} It has been used in the formation of proteoliposomes for implantation of γ-glutamyl transpeptidase into human erythrocyte membranes.{14478} Incorporation of glycosphingolipid antigens into DPPC-containing liposomes increases the immunogenicity of the antigens in mice.{14479}
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The tetracycline repressor (TetR) is a transcriptional regulator which normally binds tightly to its palindromic tetO operator DNA, blocking gene expression.{17508} Tet causes the repressor to dissociate from the DNA, allowing transcription to occur. A novel reverse TetR (revTetR) requires tetracycline as a co-repressor to bind tetO and block transcription.{17509,17510} Anhydrotetracycline (hydrochloride) is a powerful effector in both the tetracycline repressor (TetR) and reverse TetR (revTetR) systems, binding the Tet repressor 35-fold more strongly than Tet.{17508,17511} Moreover, anhydrotetracycline poorly binds the 30S ribosomal subunit, compared to Tet,{17512} so it does not act as a general inhibitor of translation and is a poor antibiotic. Perhaps related to this, the concentration of anhydrotetracycline that inhibits eukaryotic cell growth is more than a 1,000-fold above the dose that alters transcription through TetR.{17508}
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The tetracycline repressor (TetR) is a transcriptional regulator which normally binds tightly to its palindromic tetO operator DNA, blocking gene expression.{17508} Tet causes the repressor to dissociate from the DNA, allowing transcription to occur. A novel reverse TetR (revTetR) requires tetracycline as a co-repressor to bind tetO and block transcription.{17509,17510} Anhydrotetracycline (hydrochloride) is a powerful effector in both the tetracycline repressor (TetR) and reverse TetR (revTetR) systems, binding the Tet repressor 35-fold more strongly than Tet.{17508,17511} Moreover, anhydrotetracycline poorly binds the 30S ribosomal subunit, compared to Tet,{17512} so it does not act as a general inhibitor of translation and is a poor antibiotic. Perhaps related to this, the concentration of anhydrotetracycline that inhibits eukaryotic cell growth is more than a 1,000-fold above the dose that alters transcription through TetR.{17508}
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