Product Name :
CI-1040 (PD184352)
Description:
CI-1040, also known as PD184352, is a MEK inhibitor, which demonstrated in vivo activity in preclinical animal models and subsequently became the first MEK inhibitor to enter clinical trial. CI-1040 suffered however from poor exposure due to its poor solubility and rapid clearance, and as a result, development of the compound was terminated.
CAS:
212631-79-3
Molecular Weight:
478.66
Formula:
C17H14ClF2IN2O2
Chemical Name:
2-(2-Chloro-4-iodophenylamino)-N-(cyclopropylmethoxy)-3, 4-difluorobenzamide
Smiles :
O=C(NOCC1CC1)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1Cl
InChiKey:
GFMMXOIFOQCCGU-UHFFFAOYSA-N
InChi :
InChI=1S/C17H14ClF2IN2O2/c18-12-7-10(21)3-6-14(12)22-16-11(4-5-13(19)15(16)20)17(24)23-25-8-9-1-2-9/h3-7,9,22H,1-2,8H2,(H,23,24)
Purity:
≥98% (or refer to the Certificate of Analysis)
Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis
Storage Condition :
Dry, dark and -20 oC for 1 year or refer to the Certificate of Analysis.
Shelf Life:
≥12 months if stored properly.
Stock Solution Storage:
0 – 4 oC for 1 month or refer to the Certificate of Analysis.
Additional information:
CI-1040, also known as PD184352, is a MEK inhibitor, which demonstrated in vivo activity in preclinical animal models and subsequently became the first MEK inhibitor to enter clinical trial. CI-1040 suffered however from poor exposure due to its poor solubility and rapid clearance, and as a result, development of the compound was terminated.|Product information|CAS Number: 212631-79-3|Molecular Weight: 478.66|Formula: C17H14ClF2IN2O2|Synonym:|CI1040|CI 1040|PD184352|PD 184352|PD-184352|Chemical Name: 2-(2-Chloro-4-iodophenylamino)-N-(cyclopropylmethoxy)-3, 4-difluorobenzamide|Smiles: O=C(NOCC1CC1)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1Cl|InChiKey: GFMMXOIFOQCCGU-UHFFFAOYSA-N|InChi: InChI=1S/C17H14ClF2IN2O2/c18-12-7-10(21)3-6-14(12)22-16-11(4-5-13(19)15(16)20)17(24)23-25-8-9-1-2-9/h3-7,9,22H,1-2,8H2,(H,23,24)|Technical Data|Appearance: Solid Power|Purity: ≥98% (or refer to the Certificate of Analysis)|Solubility: DMSO: 96 mg/mL(200.{{Repotrectinib} medchemexpress|{Repotrectinib} ROS Kinase|{Repotrectinib} Biological Activity|{Repotrectinib} In Vivo|{Repotrectinib} supplier|{Repotrectinib} Cancer} 55 mM).{{Treosulfan} web|{Treosulfan} Cell Cycle/DNA Damage|{Treosulfan} Purity & Documentation|{Treosulfan} Formula|{Treosulfan} supplier|{Treosulfan} Autophagy} Water: Insoluble.PMID:23554582 |Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis|Storage Condition: Dry, dark and -20 oC for 1 year or refer to the Certificate of Analysis.|Shelf Life: ≥12 months if stored properly.|Stock Solution Storage: 0 – 4 oC for 1 month or refer to the Certificate of Analysis.|Drug Formulation: To be determined|HS Tariff Code: 382200|How to use|In Vitro:|CI-1040 treatment produces a reduction of pMAPK levels in multiple tumor cells including Colon 26, BX-PC3 pancreatic, A431 cervical, HT-29 colon, ZR-25-1 breast and SKOV-3 ovarian carcinomas. CI-1040 treatment doesn’t inhibit the phosphorylation of Jun kinase, p38 kinase or Akt, indicating CI-1040 specifically targets MEK. Inhibition of MAPK activation by CI-1040 prevents cell cycle progression and induces a G1 block. The IC50 for inhibition of MEK1 by CI-1040 is 0.3 μM, 15-fold higher than the concentration required to inhibit the EGF-induced activation of ERK2 in Swiss 3T3 cells. These results indicate CI-1040 exerts its effects on cells by suppressing the activation of MKK1, and not by blocking its activity. 2 nM PD184352 inhibits the activation of MKK1 in Swiss 3T3 cells by 50%, while over 100-fold concentration of CI-1040 inhibits MEK1 in vitro. PD184352 also inhibits the Raf-catalysed phosphorylation of MEK1 without any effect on the Raf-catalysed phosphorylation of myelin basic protein. CI-1040 inhibits 86% of papillary thyroid carcinoma (PTC) cell growth with the RET/PTC1 rearrangement at 10μM compared with cells treated with DMSO only. CI-1040 shows potent inhibition to PTC cells (BRAF mutation) with GI50 of 52 nM, but low activity to RET/PTC1 rearrangement type with GI50 of 1.1 μM. A recent research indicates CI-1040 increases the apoptotic effect of BMS-214662 in a CML blast crisis cell line, K562, and in primary chronic phase CD34+ CML cells.|In Vivo:|Oral dosing of CI-1040 impairs the growth of colon tumor xenografts of mouse and human with a wide dose range of 48-200 mg/kg per dose, but not of P388 leukemia. CI-1040 inhibits the tumor xenografts from PTC cells carrying a BRAF mutation with 31.3% reduction, carrying the RET/PTC1 rearrangement with 47.5% reduction than in untreated (vehicle) mice after 3 weeks of oral administration (300 mg/kg/d). No toxic effects are observed in any mice when they are treated with CI-1040. Transient exposure of mammary tumors to CI-1040 and UCN-01 causes tumor cell death in vivo and prolonged suppression of tumor regrowth. Combined treatment with CI-1040 (25 mg/kg) and UCN-01 (0.1-0.2 mg/kg) significantly reduces MDA-MB-231, and largely abolishs MCF7 tumor growth in implanted athymic mice, while either single treatment has no significant activity. The drug combination leads to profound tumor cell death which correlates with a reduction in the phosphorylation of ERK1/2 and the immuno-reactivity of Ki67 and of CD31.|References:|Henderson YC, et al. Arch Otolaryngol Head Neck Surg, 2009, 135(4), 347-354Davies SP, et al. Biochem J, 2000, 135(1), 95-105.Sebolt-Leopold JS, et al. Nat Med, 1999, 5(7), 810-816.Products are for research use only. Not for human use.|
