| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
AP-1; c-Myc
Mycro3 targets the basic helix-loop-helix leucine zipper (bHLH-LZ) domain of MYC, specifically the region involved in heterodimerization with MAX. By binding to MYC, Mycro3 prevents the formation of the MYC-MAX complex, which is required for MYC to bind to DNA and activate transcription of its target genes. This inhibition disrupts the expression of MYC target genes involved in cell cycle progression, ribosome biogenesis, and metabolism, leading to reduced cell proliferation and induction of apoptosis in MYC-dependent cancer cells. |
|---|---|
| ln Vitro |
In whole-cell experiments, Mycro 3 is a strong and sensitive c-Myc dye that exhibits a mild inhibitory effect against activator protein 1 (AP-1). The dye-reactive properties of Mycro 3 are identical to those of its predecessor. Mycro 3 prevents Myc and Max from coordinating with the c-Myc dye. Mycro 3 is a highly specific inhibitor of DNA binding and c-Myc/Max dimerization [1]. With IC50s of 0.25 and 9.0 μM for cells with intact Myc alleles and Myc-null cells, respectively, Mycro 3 shows excellent promise [2].
In vitro, Mycro3 demonstrates potent inhibition of MYC transcriptional activity in cell-based reporter assays. The compound reduces the expression of MYC target genes at both the mRNA and protein levels. Mycro3 inhibits the proliferation of MYC-driven cancer cell lines with IC₅₀ values in the low micromolar range. It induces cell cycle arrest and apoptosis in cancer cells that are dependent on MYC for survival. The compound shows selectivity for MYC-driven cells over non-MYC-driven cells. |
| ln Vivo |
In patients with pancreatic ductal adenocarcinoma (PDA), Mycro 3 (100 mg/kg; oral; taken daily for two months) significantly reduces cell swelling, enlarges the pancreas, and causes considerable shrinking. Significant differences were also observed in the growth of Mycro 3-treated NOD/SCID tumors containing orthotopic or heterotopic human pancreatic xenografts [2].
In vivo, Mycro3 has demonstrated antitumor activity in mouse xenograft models of MYC-driven cancers. Administration of Mycro3 via intraperitoneal injection or oral gavage leads to significant inhibition of tumor growth. The compound reduces the expression of MYC target genes in tumor tissues and induces apoptosis in tumor cells. Mycro3 is well-tolerated in animal studies at effective doses, with no significant body weight loss or toxicity observed. Its in vivo efficacy supports the therapeutic potential of targeting MYC for cancer treatment. |
| Enzyme Assay |
Cell-free biochemical assays for Mycro3 involve assessing its binding to the MYC protein. These assays typically use purified MYC bHLH-LZ domain and measure the compound's ability to disrupt the MYC-MAX interaction using techniques such as surface plasmon resonance (SPR), fluorescence polarization, or AlphaScreen. The compound's effects on MYC-MAX heterodimerization can also be assessed using co-immunoprecipitation or gel-shift assays.
|
| Cell Assay |
In vitro cellular assays for Mycro3 use MYC-driven cancer cell lines, such as Burkitt's lymphoma (e.g., Raji, Ramos) or neuroblastoma cells. Cells are treated with various concentrations of Mycro3 for a specified period. The compound's effects on cell proliferation are assessed using MTT, CCK-8, or BrdU incorporation assays. Apoptosis is measured by flow cytometry using Annexin V/PI staining or by assessing caspase activity. The expression of MYC target genes is measured by RT-PCR or Western blot.
|
| Animal Protocol |
Animal/Disease Models: Moribund Pdx1-cre/KRAS* mice with pancreatic ductal adenocarcinoma (PDA) [2]
Doses: 100 mg/kg Route of Administration: Oral; one time/day for two months Experimental Results: Prolonged survival . Mycro 3 administration was stopped after two months, and the mice survived for another month. In vivo animal studies for Mycro3 are conducted in mouse xenograft models of MYC-driven cancers. Immunodeficient mice are inoculated with MYC-driven tumor cells, and when tumors reach a certain size, animals are randomized to receive Mycro3 or vehicle control. Mycro3 is administered via intraperitoneal injection or oral gavage at various doses and schedules. Tumor growth is monitored by caliper measurements, and at the end of the study, tumors are collected for analysis of MYC target gene expression, apoptosis, and proliferation. |
| ADME/Pharmacokinetics |
Mycro3 has a molecular formula of C₂₂H₂₂N₄O₃S and a molecular weight of 422.50. It is a small molecule with good solubility and stability. The compound's pharmacokinetic properties include moderate oral bioavailability, a half-life suitable for once-daily dosing, and distribution to tissues including tumors. Mycro3 is metabolized primarily by the liver and excreted in urine and feces. Its pharmacokinetic profile supports further development for cancer therapy.
|
| References | |
| Additional Infomation |
Mycro3 is a specific inhibitor of the MYC oncoprotein that blocks the MYC-MAX interaction. It is used in research to study MYC biology and to develop novel cancer therapies targeting MYC. The compound represents a potential therapeutic strategy for MYC-driven cancers, which are often aggressive and have poor prognosis. Mycro3 is for research use only and not for human therapeutic use. It has been studied as a lead compound for the development of MYC inhibitors for cancer treatment.
|
| Molecular Formula |
C24H17CLF2N6O4
|
|---|---|
| Molecular Weight |
526.88
|
| Exact Mass |
526.096
|
| Elemental Analysis |
C, 54.71; H, 3.25; Cl, 6.73; F, 7.21; N, 15.95; O, 12.15
|
| CAS # |
944547-46-0
|
| Related CAS # |
944547-46-0
|
| PubChem CID |
1045147
|
| Appearance |
Light yellow to yellow solid powder
|
| Density |
1.5±0.1 g/cm3
|
| Index of Refraction |
1.680
|
| LogP |
5.52
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
8
|
| Heavy Atom Count |
37
|
| Complexity |
837
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O=C(C1=C(NC(C2C=C3N=C(C4=CC=CO4)C=C(N3N=2)C(Cl)(F)F)=O)N(C2C=CC=CC=2)N=C1)OCC
|
| InChi Key |
YPPNLSKYXDXQGD-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C24H17ClF2N6O4/c1-2-36-23(35)15-13-28-32(14-7-4-3-5-8-14)21(15)30-22(34)17-12-20-29-16(18-9-6-10-37-18)11-19(24(25,26)27)33(20)31-17/h3-13H,2H2,1H3,(H,30,34)
|
| Chemical Name |
ethyl 5-[[7-[chloro(difluoro)methyl]-5-(furan-2-yl)pyrazolo[1,5-a]pyrimidine-2-carbonyl]amino]-1-phenylpyrazole-4-carboxylate
|
| Synonyms |
Mycro3; Mycro-3; Mycro 3
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO: ~100 mg/mL (~189.8 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (4.74 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8980 mL | 9.4898 mL | 18.9797 mL | |
| 5 mM | 0.3796 mL | 1.8980 mL | 3.7959 mL | |
| 10 mM | 0.1898 mL | 0.9490 mL | 1.8980 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
|
|
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
