Related CAS #
1854901-94-2 (free base)
1854902-31-0 (sulfate)
1854902-23-0 (sulfate hydrate 2:2:1)
1854902-24-1 (sulfate hydrate 1:1:1)
Synonym
TAK-828F; TAK 828F; TAK828F;
IUPAC/Chemical Name
[ cis-3-({(5R)-5-[(7-Fluoro-1,1-dimethyl-2,3-dihydro-1H-inden-5-yl)carbamoyl]-2-methoxy-7,8-dihydro-1,6-naphthyridin-6(5H)-yl}carbonyl)cyclobutyl]acetic Acid
InChi Key
ICMFYVOUDGRBLG-VFHHBZAHSA-N
InChi Code
InChI=1S/C28H32FN3O5/c1-28(2)8-6-16-13-18(14-20(29)24(16)28)30-26(35)25-19-4-5-22(37-3)31-21(19)7-9-32(25)27(36)17-10-15(11-17)12-23(33)34/h4-5,13-15,17,25H,6-12H2,1-3H3,(H,30,35)(H,33,34)/t15-,17+,25-/m1/s1
SMILES Code
O=C(O)C[C@H]1C[C@@H](C(N2[C@@H](C(NC3=CC(CC4)=C(C(F)=C3)C4(C)C)=O)C5=C(N=C(OC)C=C5)CC2)=O)C1
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
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
Retinoic acid-related orphan receptor γt (RORγt) is a key master regulator of the differentiation and activation of IL-17 producing CD4+ Th17, CD8+ Tc17 and IL-17/IFN-γ co-producing cells (Th1/17 cells). These cells play critical roles in the pathogenesis of autoimmune diseases such as inflammatory bowel disease and multiple sclerosis. Thus, RORγt is an attractive target for the treatment of these diseases.
Additionally, TAK-828F strongly inhibited Th17, Tc17 and Th1/17 cells' differentiation from naive T cells and memory CD4+ T cells at 100 nM without affecting Th1 cells' differentiation. In addition, TAK-828F improved Th17/Treg cells' population ratio by inhibiting Th17 cells' differentiation and up-regulating Treg cells. Furthermore, TAK-828F, at 100 nM, reduced the production of Th17-related cytokines (IL-17, IL-17F and IL-22) without affecting IFN-γ production in whole blood. These results demonstrate that TAK-828F has the potent and selective inhibitory activity against RORγt both in mouse and human cells. Additionally, oral administration of TAK-828F showed promising efficacy in naive T cell transfer mouse colitis model
Preparing Stock Solutions
The following data is based on the
product
molecular weight
509.58
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 |
1: Kono M, Ochida A, Oda T, Imada T, Banno Y, Taya N, Masada S, Kawamoto T,
Yonemori K, Nara Y, Fukase Y, Yukawa T, Tokuhara H, Skene R, Sang BC, Hoffman ID,
Snell GP, Uga K, Shibata A, Igaki K, Nakamura Y, Nakagawa H, Tsuchimori N,
Yamasaki M, Shirai J, Yamamoto S. Discovery of [ cis-3-({(5
R)-5-[(7-Fluoro-1,1-dimethyl-2,3-dihydro-1
H-inden-5-yl)carbamoyl]-2-methoxy-7,8-dihydro-1,6-naphthyridin-6(5
H)-yl}carbonyl)cyclobutyl]acetic Acid (TAK-828F) as a Potent, Selective, and
Orally Available Novel Retinoic Acid Receptor-Related Orphan Receptor γt Inverse
Agonist. J Med Chem. 2018 Mar 14. doi: 10.1021/acs.jmedchem.8b00061. [Epub ahead
of print] PubMed PMID: 29510038.
2: Shibata A, Uga K, Sato T, Sagara M, Igaki K, Nakamura Y, Ochida A, Kono M,
Shirai J, Yamamoto S, Yamasaki M, Tsuchimori N. Pharmacological inhibitory
profile of TAK-828F, a potent and selective orally available RORγt inverse
agonist. Biochem Pharmacol. 2018 Jan 30;150:35-45. doi:
10.1016/j.bcp.2018.01.023. [Epub ahead of print] PubMed PMID: 29369782.
