WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H206963
CAS#: 1627929-55-8
Description: PLX51107 is a potent and selective BRD4 inhibitor or BET inhibitor with novel in vitro and in vivo pharmacologic properties that emulates or exceeds the efficacy of BCR signaling agents in preclinical models of CLL. PLX51107 binds to the acetylated lysine recognition motifs in the bromodomains of the BRD4 protein, thereby preventing the binding of BRD4 to acetylated lysines on histones. This disrupts chromatin remodeling and gene expression.
Hodoodo Cat#: H206963
Name: PLX51107
CAS#: 1627929-55-8
Chemical Formula: C26H22N4O3
Exact Mass: 438.17
Molecular Weight: 438.490
Elemental Analysis: C, 71.22; H, 5.06; N, 12.78; O, 10.95
Synonym: PLX51107; PLX-51107; PLX 51107.
IUPAC/Chemical Name: (S)-4-(6-(3,5-dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[3,2-b]pyridin-3-yl)benzoic acid
InChi Key: AMSUHYUVOVCWTP-INIZCTEOSA-N
InChi Code: InChI=1S/C26H22N4O3/c1-15-24(17(3)33-29-15)20-12-23-25(28-13-20)21(18-7-9-19(10-8-18)26(31)32)14-30(23)16(2)22-6-4-5-11-27-22/h4-14,16H,1-3H3,(H,31,32)/t16-/m0/s1
SMILES Code: O=C(O)C1=CC=C(C2=CN([C@H](C3=NC=CC=C3)C)C4=CC(C5=C(C)ON=C5C)=CN=C42)C=C1
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info: Bromodomain and extra-terminal (BET) family proteins are key regulators of gene expression in cancer. Herein, we utilize BRD4 profiling to identify critical pathways involved in pathogenesis of chronic lymphocytic leukemia (CLL). BRD4 is overexpressed in CLL and is enriched proximal to genes upregulated or de novo expressed in CLL with known functions in disease pathogenesis and progression. These genes, including key members of the B-cell receptor (BCR) signaling pathway, provide a rationale for this therapeutic approach to identify new targets in alternative types of cancer. Prevention of the expression of certain growth-promoting genes may lead to an induction of apoptosis and an inhibition of proliferation in BRD4-overexpressing tumor cells. BRD4, a member of the human bromodomain and extra-terminal (BET) family of proteins, is a transcriptional regulator that is overexpressed in certain tumor cells and plays an important role in cellular proliferation.
Biological target: | PLX51107 is a potent and selective BET inhibitor, with Kds of 1.6, 2.1, 1.7, and 5 nM for BD1 and 5.9, 6.2, 6.1, and 120 nM for BD2 of BRD2, BRD3, BRD4, and BRDT, respectively. |
In vitro activity: | The effect of PLX51107 on melanoma tumor growth and TIL (tumor-infiltrating lymphocytes) in the tumor microenvironment was tested in immune-competent, BRAF V600E mouse melanoma models: D4M3.A and YUMM3.3. PLX51107 slowed growth of D4M3.A and YUMM3.3 cells in vitro (Fig. 1A and Supplemental Fig. 1B). Similar effects were observed in human A375 and WM793 BRAF V600E melanoma cell lines. Reference: Pigment Cell Melanoma Res. 2019 Sep;32(5):687-696. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6697571/ |
In vivo activity: | PLX51107 significantly inhibited D4M3.A and YUMM3.3 tumor growth in vivo (Fig. 1B) and prolonged animal survival in mice bearing tumors (Fig. 1C). PLX51107 treatment caused 10–15% weight loss in tumor-bearing mice (Supplemental Fig. 1C); however, weight was maintained with liquid supplementation (detailed in Materials and Methods). These data suggest that BETi delays the growth of cutaneous melanoma in the presence of an intact immune system. Reference: Pigment Cell Melanoma Res. 2019 Sep;32(5):687-696. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6697571/ |
Solvent | Max Conc. mg/mL | Max Conc. mM | |
---|---|---|---|
Solubility | |||
DMSO | 50.0 | 114.00 |
The following data is based on the product molecular weight 438.49 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
---|---|---|---|
1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
Formulation protocol: | 1. Erkes DA, Field CO, Capparelli C, Tiago M, Purwin TJ, Chervoneva I, Berger AC, Hartsough EJ, Villanueva J, Aplin AE. The next-generation BET inhibitor, PLX51107, delays melanoma growth in a CD8-mediated manner. Pigment Cell Melanoma Res. 2019 Sep;32(5):687-696. doi: 10.1111/pcmr.12788. Epub 2019 May 20. PMID: 31063649; PMCID: PMC6697571. 2. Erkes DA, Rosenbaum SR, Field CO, Chervoneva I, Villanueva J, Aplin AE. PLX3397 inhibits the accumulation of intra-tumoral macrophages and improves bromodomain and extra-terminal inhibitor efficacy in melanoma. Pigment Cell Melanoma Res. 2020 Mar;33(2):372-377. doi: 10.1111/pcmr.12845. Epub 2019 Dec 11. PMID: 31696640; PMCID: PMC7028511. |
In vitro protocol: | 1. Erkes DA, Field CO, Capparelli C, Tiago M, Purwin TJ, Chervoneva I, Berger AC, Hartsough EJ, Villanueva J, Aplin AE. The next-generation BET inhibitor, PLX51107, delays melanoma growth in a CD8-mediated manner. Pigment Cell Melanoma Res. 2019 Sep;32(5):687-696. doi: 10.1111/pcmr.12788. Epub 2019 May 20. PMID: 31063649; PMCID: PMC6697571. |
In vivo protocol: | 1. Erkes DA, Field CO, Capparelli C, Tiago M, Purwin TJ, Chervoneva I, Berger AC, Hartsough EJ, Villanueva J, Aplin AE. The next-generation BET inhibitor, PLX51107, delays melanoma growth in a CD8-mediated manner. Pigment Cell Melanoma Res. 2019 Sep;32(5):687-696. doi: 10.1111/pcmr.12788. Epub 2019 May 20. PMID: 31063649; PMCID: PMC6697571. 2. Erkes DA, Rosenbaum SR, Field CO, Chervoneva I, Villanueva J, Aplin AE. PLX3397 inhibits the accumulation of intra-tumoral macrophages and improves bromodomain and extra-terminal inhibitor efficacy in melanoma. Pigment Cell Melanoma Res. 2020 Mar;33(2):372-377. doi: 10.1111/pcmr.12845. Epub 2019 Dec 11. PMID: 31696640; PMCID: PMC7028511. |
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