Synonym
LDC000067; LDC-000067; LDC 000067.
IUPAC/Chemical Name
3-[[6-(2-Methoxyphenyl)-4-pyrimidinyl]amino]benzenemethanesulfonamide
InChi Key
GGQCIOOSELPMBB-UHFFFAOYSA-N
InChi Code
InChI=1S/C18H18N4O3S/c1-25-17-8-3-2-7-15(17)16-10-18(21-12-20-16)22-14-6-4-5-13(9-14)11-26(19,23)24/h2-10,12H,11H2,1H3,(H2,19,23,24)(H,20,21,22)
SMILES Code
O=S(CC1=CC=CC(NC2=NC=NC(C3=CC=CC=C3OC)=C2)=C1)(N)=O
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 (50mg/mL).
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
Biological target:
LDC000067 is a highly selective CDK9 inhibitor with an IC50 value of 44±10 nM in vitro.
In vitro activity:
Multiple MB cell lines were treated with different doses of LDC067 for 72 h and cell growth was measured by MTT assay. The study found that inhibition of CDK9 decreased cell growth in a dose-dependent manner in all five different MB cell lines (Fig. 3A). Further, the study found that treatment of MB cells with LDC067 reduce its downstream target pRNA pol II ser2 level (Fig. 3B). As observed by others, LDC067 did not alter the expression of CDK9, suggesting it only suppresses CDK9 activity and not expression.
Reference: Biochem Biophys Res Commun. 2019 Dec 3;520(2):250-256. https://pubmed.ncbi.nlm.nih.gov/31594641/
In vivo activity:
Oil Red O staining in the entire aorta showed that the plaque area markedly increased in the HFD-mice compared to the STD-mice, and the increased lesion area were notably reduced by treatment with LDC000067 (both low and high doses) (Figure 2A–2B). As depicted in Figure 2C–2D and Supplementary Figure 2A, the plaque areas in the aortic sinus of LDC000067-treated mice were dramatically smaller than that of the vehicle-treated HFD-fed mice. Masson’s trichome staining showed similar results in reduced collagen deposition (Figure 2E and Supplementary Figure 2B).
Reference: Aging (Albany NY). 2021 Jun 8;13(undefined). https://www.aging-us.com/full/202998
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
34.7 |
93.62 |
| DMSO:PBS (pH 7.2) (1:1) |
0.5 |
1.35 |
| DMF |
20.0 |
53.99 |
| Ethanol |
2.0 |
5.40 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
370.43
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. Song H, Bhakat R, Kling MJ, Coulter DW, Chaturvedi NK, Ray S, Joshi SS. Targeting cyclin-dependent kinase 9 sensitizes medulloblastoma cells to chemotherapy. Biochem Biophys Res Commun. 2019 Dec 3;520(2):250-256. doi: 10.1016/j.bbrc.2019.09.118. Epub 2019 Oct 5. PMID: 31594641.
2. Wang J, Dean DC, Hornicek FJ, Shi H, Duan Z. Cyclin-dependent kinase 9 (CDK9) is a novel prognostic marker and therapeutic target in ovarian cancer. FASEB J. 2019 May;33(5):5990-6000. doi: 10.1096/fj.201801789RR. Epub 2019 Feb 6. PMID: 30726104; PMCID: PMC6463912.
3. Huang S, Luo W, Wu G, Shen Q, Zhuang Z, Yang D, Qian J, Hu X, Cai Y, Chattipakorn N, Huang W, Liang G. Inhibition of CDK9 attenuates atherosclerosis by inhibiting inflammation and phenotypic switching of vascular smooth muscle cells. Aging (Albany NY). 2021 Jun 8;13(undefined). doi: 10.18632/aging.202998. Epub ahead of print. PMID: 34102609.
4. Yang X, Luo W, Li L, Hu X, Xu M, Wang Y, Feng J, Qian J, Guan X, Zhao Y, Liang G. CDK9 inhibition improves diabetic nephropathy by reducing inflammation in the kidneys. Toxicol Appl Pharmacol. 2021 Apr 1;416:115465. doi: 10.1016/j.taap.2021.115465. Epub 2021 Feb 22. PMID: 33631230.
In vitro protocol:
1. Song H, Bhakat R, Kling MJ, Coulter DW, Chaturvedi NK, Ray S, Joshi SS. Targeting cyclin-dependent kinase 9 sensitizes medulloblastoma cells to chemotherapy. Biochem Biophys Res Commun. 2019 Dec 3;520(2):250-256. doi: 10.1016/j.bbrc.2019.09.118. Epub 2019 Oct 5. PMID: 31594641.
2. Wang J, Dean DC, Hornicek FJ, Shi H, Duan Z. Cyclin-dependent kinase 9 (CDK9) is a novel prognostic marker and therapeutic target in ovarian cancer. FASEB J. 2019 May;33(5):5990-6000. doi: 10.1096/fj.201801789RR. Epub 2019 Feb 6. PMID: 30726104; PMCID: PMC6463912.
In vivo protocol:
1. Huang S, Luo W, Wu G, Shen Q, Zhuang Z, Yang D, Qian J, Hu X, Cai Y, Chattipakorn N, Huang W, Liang G. Inhibition of CDK9 attenuates atherosclerosis by inhibiting inflammation and phenotypic switching of vascular smooth muscle cells. Aging (Albany NY). 2021 Jun 8;13(undefined). doi: 10.18632/aging.202998. Epub ahead of print. PMID: 34102609.
2. Yang X, Luo W, Li L, Hu X, Xu M, Wang Y, Feng J, Qian J, Guan X, Zhao Y, Liang G. CDK9 inhibition improves diabetic nephropathy by reducing inflammation in the kidneys. Toxicol Appl Pharmacol. 2021 Apr 1;416:115465. doi: 10.1016/j.taap.2021.115465. Epub 2021 Feb 22. PMID: 33631230.
1: Xue S, Shao Q, Zhu LB, Jiang YF, Wang C, Xue B, Lu HM, Sang WL, Ma JZ. LDC000067 suppresses RANKL-induced osteoclastogenesis in vitro and prevents LPS-induced osteolysis in vivo. Int Immunopharmacol. 2019 Oct;75:105826. doi: 10.1016/j.intimp.2019.105826. Epub 2019 Aug 19. PubMed PMID: 31437791.
2: Xue S, Zhu L, Wang C, Jiang Y, Lu H, Liu Y, Shao Q, Xue B, Sang W, Ma J. CDK9 attenuation exerts protective effects on catabolism and hypertrophy in chondrocytes and ameliorates osteoarthritis development. Biochem Biophys Res Commun. 2019 Sep 10;517(1):132-139. doi: 10.1016/j.bbrc.2019.07.032. Epub 2019 Jul 13. PubMed PMID: 31307784.
3: Wang J, Dean DC, Hornicek FJ, Shi H, Duan Z. Cyclin-dependent kinase 9 (CDK9) is a novel prognostic marker and therapeutic target in ovarian cancer. FASEB J. 2019 May;33(5):5990-6000. doi: 10.1096/fj.201801789RR. Epub 2019 Feb 6. PubMed PMID: 30726104; PubMed Central PMCID: PMC6463912.
4: Löschmann N, Michaelis M, Rothweiler F, Voges Y, Balónová B, Blight BA, Cinatl J Jr. ABCB1 as predominant resistance mechanism in cells with acquired SNS-032 resistance. Oncotarget. 2016 Sep 6;7(36):58051-58064. doi: 10.18632/oncotarget.11160. PubMed PMID: 27517323; PubMed Central PMCID: PMC5295411.
5: Albert TK, Rigault C, Eickhoff J, Baumgart K, Antrecht C, Klebl B, Mittler G, Meisterernst M. Characterization of molecular and cellular functions of the cyclin-dependent kinase CDK9 using a novel specific inhibitor. Br J Pharmacol. 2014 Jan;171(1):55-68. doi: 10.1111/bph.12408. PubMed PMID: 24102143; PubMed Central PMCID: PMC3874696.
