Synonym
Olumacostat glasaretil; DRM01B; DRM-01B; DRM 01B.
IUPAC/Chemical Name
2-((2-ethoxy-2-oxoethyl)(methyl)amino)-2-oxoethyl 5-(tetradecyloxy)furan-2-carboxylate
InChi Key
FYJLDICZGDFWKP-UHFFFAOYSA-N
InChi Code
InChI=1S/C26H43NO7/c1-4-6-7-8-9-10-11-12-13-14-15-16-19-32-25-18-17-22(34-25)26(30)33-21-23(28)27(3)20-24(29)31-5-2/h17-18H,4-16,19-21H2,1-3H3
SMILES Code
O=C(C1=CC=C(OCCCCCCCCCCCCCC)O1)OCC(N(CC(OCC)=O)C)=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, not in water
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
Inhibition of ACC activity in the sebaceous glands is designed to substantially impact sebum production since over 80% of human sebum components contain fatty acids. OG inhibits de novo lipid synthesis in primary and transformed human sebocytes.
Biological target:
Olumacostat glasaretil is a small molecule inhibitor of acetyl coenzyme A carboxylase (ACC).
In vitro activity:
Stimulation of primary human sebocytes with insulin plus the LXR agonist T0901317 increased fatty acid synthesis by 2.4-fold, as evidenced by 14C-acetate incorporation (Figure 1). Treatment with olumacostat glasaretil (OG) lowered 14C-acetate incorporation in the presence of these stimuli. At 3 μmol/L, OG reduced fatty acid synthesis to baseline or below baseline levels. Dose-dependent inhibition of de novo lipid synthesis was also observed in SEB-1 cells. 14C-acetate incorporation levels were 85–90% lower for SEB-1 cultures treated with OG at 20 μmol/L compared with control samples.
Reference: J Invest Dermatol. 2017 Jul;137(7):1415-1423. https://www.jidonline.org/article/S0022-202X(17)30186-0/fulltext
In vivo activity:
Topical application of OG (6% w/w) significantly reduced hamster ear sebaceous gland size when applied twice daily for 14 days (21.4 ± 12.7%), once daily for 21 days (16.5 ± 17.6%), or twice daily for 21 days (20.4 ± 10.1%) (Figure 4a). With OG treatment, sebaceous glands were generally less lobular in appearance (Figure 4b and c). The ear sebaceous gland area for hamsters treated with OG gel (7.5% w/w) daily for 3 weeks was 15.3 ± 7.3% lower than for placebo gel-treated animals (P < 0.05). OG 1% gel reduced sebaceous gland size by 11.0 ± 16.2%, although this was not statistically significant. Histologically, neither epidermal or stratum corneum changes nor a presence of inflammatory cells were evident within ear sample cross-sections from OG-treated animals, suggesting that topically-applied OG was well tolerated.
Reference: J Invest Dermatol. 2017 Jul;137(7):1415-1423. https://www.jidonline.org/article/S0022-202X(17)30186-0/fulltext
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
125.0 |
259.54 |
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
481.63
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. Hunt DW, Winters GC, Brownsey RW, Kulpa JE, Gilliland KL, Thiboutot DM, Hofland HE. Inhibition of Sebum Production with the Acetyl Coenzyme A Carboxylase Inhibitor Olumacostat Glasaretil. J Invest Dermatol. 2017 Jul;137(7):1415-1423. doi: 10.1016/j.jid.2016.12.031. Epub 2017 Mar 1. PMID: 28259683.
In vitro protocol:
1. Hunt DW, Winters GC, Brownsey RW, Kulpa JE, Gilliland KL, Thiboutot DM, Hofland HE. Inhibition of Sebum Production with the Acetyl Coenzyme A Carboxylase Inhibitor Olumacostat Glasaretil. J Invest Dermatol. 2017 Jul;137(7):1415-1423. doi: 10.1016/j.jid.2016.12.031. Epub 2017 Mar 1. PMID: 28259683.
In vivo protocol:
1. Hunt DW, Winters GC, Brownsey RW, Kulpa JE, Gilliland KL, Thiboutot DM, Hofland HE. Inhibition of Sebum Production with the Acetyl Coenzyme A Carboxylase Inhibitor Olumacostat Glasaretil. J Invest Dermatol. 2017 Jul;137(7):1415-1423. doi: 10.1016/j.jid.2016.12.031. Epub 2017 Mar 1. PMID: 28259683.
1: Cong TX, Hao D, Wen X, Li XH, He G, Jiang X. From pathogenesis of acne vulgaris to anti-acne agents. Arch Dermatol Res. 2019 Jul;311(5):337-349. doi: 10.1007/s00403-019-01908-x. Epub 2019 Mar 11. PMID: 30859308.
2: Endly DC, Miller RA. Oily Skin: A review of Treatment Options. J Clin Aesthet Dermatol. 2017 Aug;10(8):49-55. Epub 2017 Aug 1. PMID: 28979664; PMCID: PMC5605215.
3: Melnik BC. Olumacostat Glasaretil, a Promising Topical Sebum-Suppressing Agent that Affects All Major Pathogenic Factors of Acne Vulgaris. J Invest Dermatol. 2017 Jul;137(7):1405-1408. doi: 10.1016/j.jid.2017.01.026. PMID: 28647025.
4: Zouboulis CC, Dessinioti C, Tsatsou F, Gollnick HPM. Anti-acne drugs in phase 1 and 2 clinical trials. Expert Opin Investig Drugs. 2017 Jul;26(7):813-823. doi: 10.1080/13543784.2017.1337745. Epub 2017 Jun 19. PMID: 28627277.
5: Hunt DW, Winters GC, Brownsey RW, Kulpa JE, Gilliland KL, Thiboutot DM, Hofland HE. Inhibition of Sebum Production with the Acetyl Coenzyme A Carboxylase Inhibitor Olumacostat Glasaretil. J Invest Dermatol. 2017 Jul;137(7):1415-1423. doi: 10.1016/j.jid.2016.12.031. Epub 2017 Mar 1. PMID: 28259683.
6: Bissonnette R, Poulin Y, Drew J, Hofland H, Tan J. Olumacostat glasaretil, a novel topical sebum inhibitor, in the treatment of acne vulgaris: A phase IIa, multicenter, randomized, vehicle-controlled study. J Am Acad Dermatol. 2017 Jan;76(1):33-39. doi: 10.1016/j.jaad.2016.08.053. Epub 2016 Oct 28. PMID: 28029390.
