OICR-9429

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OICR-9429

本产品不向个人销售，仅用作科学研究，不用于任何人体实验及非科研性质的动物实验。

CAS NO:

1801787-56-3

OICR-9429 是一种高亲和力的 WD 重复域 5 (WDR5) 抑制剂，通过结合 WDR5 的中心肽结合袋，竞争性地阻断 WDR5 与 MLL 蛋白的相互作用。OICR-9429 可抑制组蛋白 H3K4 三甲基化，可用于非 MLL 重排白血病、结肠癌、胰腺癌、前列腺癌、膀胱癌 (BCa) 等多种癌症的研究。

生物活性

OICR-9429 is high affinityWD repeat domain 5 (WDR5)inhibitor, competitively blocks WDR5 interaction with MLL protein via binding the central peptide-binding pocket of WDR5. OICR-9429 can suppress histone H3K4 trimethylation and can be used for the research of various cancers including non-MLL-rearranged leukaemia, colon, pancreatic, prostatecancerand bladdercancer(BCa)^[1].

IC₅₀& Target

IC50: 67.74 μM (T24 cell); 0.41 μM (UM-UC-3 cell); 121.42 μM (TCCSUP)^[1]

体外研究
(In Vitro)

OICR-9429 (0-10 μM, 48 h) shows high sensitivity for T24, UM-UC-3 with IC₅₀values of 67.74 μM and 70.41 μM, respectively^[1].
OICR-9429 (0-10 μM, 48 h) shows low sensitivity for TCCSUP with IC₅₀values of 121.42 μM^[1].
OICR-9429 (70 μM, 120 μM, 140 μM and 240 μM; 48 h) reduces BCa cell viability by decreasing WDR5-mediated H3K4me3^[1].
OICR-9429 (70 μM, 120 μM, 140 μM and 240 μM; 48 h) inhibits the proliferation of BCa cells by regulating the G1/S phase transition^[1].
OICR-9429 (70 μM, 120 μM, 140 μM and 240 μM; 24 h) enhances apoptosis of BCa cells in a time-dependent and dose-dependent manner and promotes cisplatin chemosensitivity in BCa cells^[1].
OICR-9429 (70 μM, 120 μM, 140 μM and 240 μM; 24 h, 48 h) suppresses the metastatic behaviour of bladder cancer cells^[1].
OICR-9429 (70 μM, 120 μM, 140 μM and 240 μM; 48 h) suppresses PD-L1 expression induced by IFN-γ in BCa cells^[1].

Cell Proliferation Assay^[1]

Cell Line:	BCa cell lines (T24, UM-UC-3 and TCCSUP)
Concentration:	70 μM, 120 μM, 140 μM and 240 μM
Incubation Time:	5 days
Result:	Had a low proliferation rate and remarkably reduced the number of colonies formed by the three BCa cell lines in a dose-dependent manner.

Cell Cytotoxicity Assay^[1]

Cell Line:	BCa cell lines (T24, UM-UC-3 and TCCSUP)
Concentration:	0-10 μM
Incubation Time:	48 h
Result:	Inhibited cell viability in a dose-dependent manner in BCa cell lines.

Apoptosis Analysis^[1]

Cell Line:	BCa cell lines (T24, UM-UC-3 and TCCSUP)
Concentration:	70 μM, 120 μM, 140 μM and 240 μM
Incubation Time:	24 h
Result:	Showed no obvious apoptotic cells for 24 h but the apoptotic rate was significantly increased at 72 h and upregulated caspase 3/7 activity.

Cell Migration Assay^[1]

Cell Line:	BCa cell lines (T24, UM-UC-3 and TCCSUP)
Concentration:	70 μM, 120 μM, 140 μM and 240 μM
Incubation Time:	24 h, 48 h
Result:	Reduced the migratory speed and decreased the migration of the three BCa cell lines.

Cell Invasion Assay^[1]

Cell Line:	BCa cell lines (T24, UM-UC-3 and TCCSUP)
Concentration:	70 μM, 120 μM, 140 μM and 240 μM
Incubation Time:	24 h, 48 h
Result:	Decreased the invasion of the three BCa cell lines.

Western Blot Analysis^[1]

Cell Line:	BCa cell lines (T24, UM-UC-3 and TCCSUP)
Concentration:	70 μM, 120 μM, 140 μM and 240 μM
Incubation Time:	48 h
Result:	Showed significant downregulation of H3K4me3 in treated cells but not WDR5 or total H3. Reduced the expression of PD-L1 induced by IFN-γ in a dose-dependent manner at both the RNA and protein levels.

RT-PCR^[1]

Cell Line:	BCa cell lines (T24, UM-UC-3 and TCCSUP)
Concentration:	70 μM, 120 μM, 140 μM and 240 μM
Incubation Time:	48 h
Result:	Downregulated some genes related to the cell cycle, such as CDK1, PLK1, CCNE2, CCNB1, CCNA2, AURKA, and E2F1, genes related to apoptosis and DNA repair, such as BIRC5, XRCC2, AURKA, E2F1, and MCM2, and genes related to metastasis, such as AURKA and FOXM1.

Cell Cycle Analysis^[1]

Cell Line:	BCa cell lines (T24, UM-UC-3 and TCCSUP)
Concentration:	70 μM, 120 μM, 140 μM and 240 μM
Incubation Time:	48 h
Result:	Increased the cell population in the G0/G1 phase of three BCa cells and reduced cell population in the S and G2/M phases.

体内研究
(In Vivo)

OICR-9429 (30 mg/kg or 60 mg/kg, i.p) targeting WDR5 not only suppressed tumour proliferation and enhance the efficacy of cisplatin for BCa cells in vivo but also reduced the toxicity and side effects for normal tissues^[1].

Animal Model:	xenograft mouse model^[1]
Dosage:	30 mg/kg, 60 mg/kg
Administration:	30 mg/kg, 60 mg/kg, i.p.
Result:	Suppressed tumour growth, small tumours and enhanced tumour sensitivity.

分子量

555.59

性状

Solid

Formula

C₂₉H₃₂F₃N₅O₃

CAS 号

1801787-56-3

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

溶解性数据

In Vitro:

DMSO : ≥ 32 mg/mL(57.60 mM)

*"≥" means soluble, but saturation unknown.

配制储备液

浓度溶剂体积质量

1 mg

5 mg

10 mg

1 mM	1.7999 mL	8.9994 mL	17.9989 mL
5 mM	0.3600 mL	1.7999 mL	3.5998 mL
10 mM	0.1800 mL	0.8999 mL	1.7999 mL

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

1.
请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline
Solubility: ≥ 2.5 mg/mL (4.50 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (4.50 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。
将 0.9 g 氯化钠，完全溶解于 100 mL ddH2O 中，得到澄清透明的生理盐水溶液
2.
请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline)
Solubility: ≥ 2.5 mg/mL (4.50 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (4.50 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。
将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
3.
请依序添加每种溶剂： 10% DMSO 90%corn oil
Solubility: ≥ 2.5 mg/mL (4.50 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (4.50 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。
以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

*以上所有助溶剂都可在本网站选购。