Synonym
AGN 194310; AGN194310; AGN-194310; VTP-194310; VTP 194310; VTP194310;
IUPAC/Chemical Name
4-((4-(4-ethylphenyl)-2,2-dimethyl-2H-thiochromen-6-yl)ethynyl)benzoic acid
InChi Key
LHUPKWKWYWOMSK-UHFFFAOYSA-N
InChi Code
InChI=1S/C28H24O2S/c1-4-19-7-12-22(13-8-19)25-18-28(2,3)31-26-16-11-21(17-24(25)26)6-5-20-9-14-23(15-10-20)27(29)30/h7-18H,4H2,1-3H3,(H,29,30)
SMILES Code
O=C(O)C1=CC=C(C#CC2=CC(C(C3=CC=C(CC)C=C3)=CC(C)(C)S4)=C4C=C2)C=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, 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
Biological target:
AGN 194310 (VTP-194310) is a retinioic acid receptors (RARs) pan-antagonist with Kd values of 3 nM, 2 nM, 5 nM for RARα, RARβ, RARγ, respectively.
In vitro activity:
The effects of AGN 194310, a retinoic acid receptor pan-antagonist, on CD38 expression of human hematopoietic cells was evaluated. Normal cells (cord blood derived CD34+ cells) and abnormal cells (myeloid leukemic lines) were studied when grown in either serum-containing or serum-free media. The results showed that both serum and ATRA (all-trans retinoic acid) enhanced differentiation and, thereby, reduced the proportion of CD34+ CD38- cells and total CD34+ cell expansion. AGN reversed these effects of serum and ATRA: it delayed differentiation and increased CD34+ CD38- cells. These results suggest that physiological ATRA levels in serum may prevent efficient cell expansion. AGN, by neutralizing ATRA, improves cell expansion in serum-containing cultures.
Reference: Leuk Lymphoma. 2004 May;45(5):1025-35. https://www.tandfonline.com/doi/abs/10.1080/10428190310001645924
In vivo activity:
Mice were treated with AGN194310, a synthetic retinoid that antagonises the physiological function of the three RAR isotypes (alpha, beta, gamma) but does not interact with RXRs. Analyses of the granulocytic lineage using Gr-1, c-Kit and CD11b antibodies, demonstrated that granulocyte numbers were strikingly increased across haemopoietic compartments in all AGN194310-treated mice. A significant increase in the frequency of progenitor cells containing granulocytes was observed in the bone marrow of mice following treatment with AGN194310. These data demonstrate an essential role for RAR signalling in regulating the numbers of granulocytic precursors in vivo.
Reference: Leukemia. 2002 Sep;16(9):1763-72. https://www.nature.com/articles/2402625
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
50.0 |
117.77 |
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
424.56
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. Prus E, Chandraratna RA, Fibach E. Retinoic acid receptor antagonist inhibits CD38 antigen expression on human hematopoietic cells in vitro. Leuk Lymphoma. 2004 May;45(5):1025-35. doi: 10.1080/10428190310001645924. PMID: 15291363.
2. Hammond LA, Van Krinks CH, Durham J, Tomkins SE, Burnett RD, Jones EL, Chandraratna RA, Brown G. Antagonists of retinoic acid receptors (RARs) are potent growth inhibitors of prostate carcinoma cells. Br J Cancer. 2001 Aug 3;85(3):453-62. doi: 10.1054/bjoc.2001.1939. PMID: 11487280; PMCID: PMC2364081.
3. Walkley CR, Yuan YD, Chandraratna RA, McArthur GA. Retinoic acid receptor antagonism in vivo expands the numbers of precursor cells during granulopoiesis. Leukemia. 2002 Sep;16(9):1763-72. doi: 10.1038/sj.leu.2402625. PMID: 12200692.
In vitro protocol:
1. Prus E, Chandraratna RA, Fibach E. Retinoic acid receptor antagonist inhibits CD38 antigen expression on human hematopoietic cells in vitro. Leuk Lymphoma. 2004 May;45(5):1025-35. doi: 10.1080/10428190310001645924. PMID: 15291363.
2. Hammond LA, Van Krinks CH, Durham J, Tomkins SE, Burnett RD, Jones EL, Chandraratna RA, Brown G. Antagonists of retinoic acid receptors (RARs) are potent growth inhibitors of prostate carcinoma cells. Br J Cancer. 2001 Aug 3;85(3):453-62. doi: 10.1054/bjoc.2001.1939. PMID: 11487280; PMCID: PMC2364081.
In vivo protocol:
1. Walkley CR, Yuan YD, Chandraratna RA, McArthur GA. Retinoic acid receptor antagonism in vivo expands the numbers of precursor cells during granulopoiesis. Leukemia. 2002 Sep;16(9):1763-72. doi: 10.1038/sj.leu.2402625. PMID: 12200692.
1: Lind T, Sundqvist A, Hu L, Pejler G, Andersson G, Jacobson A, Melhus H. Vitamin a is a negative regulator of osteoblast mineralization. PLoS One. 2013 Dec 10;8(12):e82388. doi: 10.1371/journal.pone.0082388. eCollection 2013. PubMed PMID: 24340023; PubMed Central PMCID: PMC3858291.
2: Prus E, Chandraratna RA, Fibach E. Retinoic acid receptor antagonist inhibits CD38 antigen expression on human hematopoietic cells in vitro. Leuk Lymphoma. 2004 May;45(5):1025-35. PubMed PMID: 15291363.
3: Keedwell RG, Zhao Y, Hammond LA, Wen K, Qin S, Atangan LI, Shurland DL, Wallace DM, Bird R, Reitmair A, Chandraratna RA, Brown G. An antagonist of retinoic acid receptors more effectively inhibits growth of human prostate cancer cells than normal prostate epithelium. Br J Cancer. 2004 Aug 2;91(3):580-8. PubMed PMID: 15266311; PubMed Central PMCID: PMC2409843.
4: Austenaa LM, Carlsen H, Ertesvag A, Alexander G, Blomhoff HK, Blomhoff R. Vitamin A status significantly alters nuclear factor-kappaB activity assessed by in vivo imaging. FASEB J. 2004 Aug;18(11):1255-7. Epub 2004 Jun 4. PubMed PMID: 15180954.
5: Walkley CR, Yuan YD, Chandraratna RA, McArthur GA. Retinoic acid receptor antagonism in vivo expands the numbers of precursor cells during granulopoiesis. Leukemia. 2002 Sep;16(9):1763-72. PubMed PMID: 12200692.
6: Weston AD, Chandraratna RA, Torchia J, Underhill TM. Requirement for RAR-mediated gene repression in skeletal progenitor differentiation. J Cell Biol. 2002 Jul 8;158(1):39-51. Epub 2002 Jul 8. PubMed PMID: 12105181; PubMed Central PMCID: PMC2173026.
7: Hammond LA, Van Krinks CH, Durham J, Tomkins SE, Burnett RD, Jones EL, Chandraratna RA, Brown G. Antagonists of retinoic acid receptors (RARs) are potent growth inhibitors of prostate carcinoma cells. Br J Cancer. 2001 Aug 3;85(3):453-62. PubMed PMID: 11487280; PubMed Central PMCID: PMC2364081.
8: Johnson AT, Wang L, Standeven AM, Escobar M, Chandraratna RA. Synthesis and biological activity of high-affinity retinoic acid receptor antagonists. Bioorg Med Chem. 1999 Jul;7(7):1321-38. PubMed PMID: 10465407.
