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MedKoo Cat#: 573428 | Name: Adavivint
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Adavivint, also known as SM04690, is a small-molecule inhibitor of the Wnt pathway which is being investigated as a potential disease modifying agent for the treatment of osteoarthritis of the knee. It modulates the Wnt signaling pathway by inhibiting CDC-like kinase 2 and dual-specificity tyrosine phosphorylation-regulated kinase 1 A which are molecular regulators in Wnt signaling, chondrogenesis, and inflammation.

Chemical Structure

Adavivint
Adavivint
CAS#1467093-03-3 (free base)

Theoretical Analysis

MedKoo Cat#: 573428

Name: Adavivint

CAS#: 1467093-03-3 (free base)

Chemical Formula: C29H24FN7O

Exact Mass: 505.2026

Molecular Weight: 505.56

Elemental Analysis: C, 68.90; H, 4.79; F, 3.76; N, 19.39; O, 3.16

Price and Availability

Size Price Availability Quantity
10mg USD 150.00 Ready to ship
25mg USD 250.00 Ready to ship
50mg USD 450.00 Ready to ship
100mg USD 750.00 Ready to ship
200mg USD 1,350.00 Ready to ship
500mg USD 2,850.00 Ready to ship
1g USD 3,850.00 Ready to ship
2g USD 6,450.00 2 Weeks
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Related CAS #
1467093-03-3 (free base) Adavivint HCl
Synonym
Adavivint; SM-04690; SM04690; SM 04690; LORECIVIVINT;
IUPAC/Chemical Name
N-(5-(3-(7-(3-Fluorophenyl)-3H-imidazo(4,5-C)pyridin-2-yl)-1H-indazol-5- yl)-pyridin-3-yl)-3-methylbutanamide
InChi Key
AQDWDWAYVBQMAM-UHFFFAOYSA-N
InChi Code
1S/C29H24FN7O/c1-16(2)8-26(38)33-21-10-19(12-31-13-21)17-6-7-24-22(11-17)28(37-36-24)29-34-25-15-32-14-23(27(25)35-29)18-4-3-5-20(30)9-18/h3-7,9-16H,8H2,1-2H3,(H,33,38)(H,34,35)(H,36,37)
SMILES Code
CC(C)CC(=O)Nc1cncc(c1)c2ccc3[nH]nc(c4nc5c(cncc5[nH]4)c6cccc(F)c6)c3c2
Appearance
Solid powder
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
>3 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
Biological target:
Adavivint (SM04690; Lorecivivint) is an inhibitor of canonical Wnt signaling, with an EC50 of 19.5 nM via a high-throughput TCF/LEF-reporter assay in SW480 colon cancer cells.
In vitro activity:
SM04690 induced a robust apoptotic response in HEC108 cells (Ctrl, 0.65% vs. 128 nmol/L 28.5% Annexin V/PI positive). With respect to proliferation, SM04690 significantly inhibited BrdU incorporation and an exceptional inhibition in the HEC265 cell lines. These data highlight that the CTNNB1-mutant cells lines are more sensitive to SM04690. The source of this sensitivity does seem to vary among cell lines, with HEC108 demonstrating a proapoptotic response and HEC265 demonstrating an antiproliferative response, likely due to each cell line's larger mutational profile. Reference: Mol Carcinog. 2021 May 26. doi: 10.1002/mc.23308. https://pubmed.ncbi.nlm.nih.gov/34038589/
In vivo activity:
The efficacy of a single intradiscal injection of LOR (Adavivint) (0.33 µg) or vehicle was evaluated in the needle-puncture model of DDD (degenerative disc disease). Radiographic measurement of disc heights showed a DHI of 0.12±0.01 prior to injury. One week after needle-puncture surgery and prior to treatment of the NP of injured discs, DHI was reduced to 0.095±0.01 (~80% of baseline). Five weeks after dosing (6 weeks post injury), disc height was further reduced (DHI=0.083±0.01; ~68% of baseline and ~87% of Week 1) in vehicle-treated rats. Five weeks after dosing, disc height (ie, DHI) was maintained (DHI=0.096±0.01; ~80% of baseline and ~101.6% of Week 1) in LOR-treated rats and was significantly (p=.012) higher than that in vehicle-treated rats. When disc height was measured using quantitative histomorphometric analysis, LOR-treated rats demonstrated greater disc heights (789.6±15.8 µm) than vehicle-treated rats (692.7±11.6 µm). Reference: Osteoarthritis Cartilage. 2018 Jan;26(1):18-27. https://pubmed.ncbi.nlm.nih.gov/32413487/
Solvent mg/mL mM
Solubility
DMSO 27.5 54.40
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 505.56 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.

Recalculate based on batch purity %
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. Moroney MR, Woodruff E, Qamar L, Bradford AP, Wolsky R, Bitler BG, Corr BR. Inhibiting Wnt/beta-catenin in CTNNB1-mutated endometrial cancer. Mol Carcinog. 2021 May 26. doi: 10.1002/mc.23308. Epub ahead of print. PMID: 34038589. 2. Deshmukh V, O'Green AL, Bossard C, Seo T, Lamangan L, Ibanez M, Ghias A, Lai C, Do L, Cho S, Cahiwat J, Chiu K, Pedraza M, Anderson S, Harris R, Dellamary L, Kc S, Barroga C, Melchior B, Tam B, Kennedy S, Tambiah J, Hood J, Yazici Y. Modulation of the Wnt pathway through inhibition of CLK2 and DYRK1A by lorecivivint as a novel, potentially disease-modifying approach for knee osteoarthritis treatment. Osteoarthritis Cartilage. 2019 Sep;27(9):1347-1360. doi: 10.1016/j.joca.2019.05.006. Epub 2019 May 25. PMID: 31132406. 3. Deshmukh V, Ibanez M, Hu H, Cahiwat J, Wei Y, Stewart J, Hood J, Yazici Y. A small-molecule inhibitor of the Wnt pathway, lorecivivint (SM04690), as a potential disease-modifying agent for the treatment of degenerative disc disease. Spine J. 2020 Sep;20(9):1492-1502. doi: 10.1016/j.spinee.2020.04.024. Epub 2020 May 12. PMID: 32413487. 4. Deshmukh V, Hu H, Barroga C, Bossard C, Kc S, Dellamary L, Stewart J, Chiu K, Ibanez M, Pedraza M, Seo T, Do L, Cho S, Cahiwat J, Tam B, Tambiah JRS, Hood J, Lane NE, Yazici Y. A small-molecule inhibitor of the Wnt pathway (SM04690) as a potential disease modifying agent for the treatment of osteoarthritis of the knee. Osteoarthritis Cartilage. 2018 Jan;26(1):18-27. doi: 10.1016/j.joca.2017.08.015. Epub 2017 Sep 6. PMID: 28888902.
In vitro protocol:
1. Moroney MR, Woodruff E, Qamar L, Bradford AP, Wolsky R, Bitler BG, Corr BR. Inhibiting Wnt/beta-catenin in CTNNB1-mutated endometrial cancer. Mol Carcinog. 2021 May 26. doi: 10.1002/mc.23308. Epub ahead of print. PMID: 34038589. 2. Deshmukh V, O'Green AL, Bossard C, Seo T, Lamangan L, Ibanez M, Ghias A, Lai C, Do L, Cho S, Cahiwat J, Chiu K, Pedraza M, Anderson S, Harris R, Dellamary L, Kc S, Barroga C, Melchior B, Tam B, Kennedy S, Tambiah J, Hood J, Yazici Y. Modulation of the Wnt pathway through inhibition of CLK2 and DYRK1A by lorecivivint as a novel, potentially disease-modifying approach for knee osteoarthritis treatment. Osteoarthritis Cartilage. 2019 Sep;27(9):1347-1360. doi: 10.1016/j.joca.2019.05.006. Epub 2019 May 25. PMID: 31132406.
In vivo protocol:
1. Deshmukh V, Ibanez M, Hu H, Cahiwat J, Wei Y, Stewart J, Hood J, Yazici Y. A small-molecule inhibitor of the Wnt pathway, lorecivivint (SM04690), as a potential disease-modifying agent for the treatment of degenerative disc disease. Spine J. 2020 Sep;20(9):1492-1502. doi: 10.1016/j.spinee.2020.04.024. Epub 2020 May 12. PMID: 32413487. 2. Deshmukh V, Hu H, Barroga C, Bossard C, Kc S, Dellamary L, Stewart J, Chiu K, Ibanez M, Pedraza M, Seo T, Do L, Cho S, Cahiwat J, Tam B, Tambiah JRS, Hood J, Lane NE, Yazici Y. A small-molecule inhibitor of the Wnt pathway (SM04690) as a potential disease modifying agent for the treatment of osteoarthritis of the knee. Osteoarthritis Cartilage. 2018 Jan;26(1):18-27. doi: 10.1016/j.joca.2017.08.015. Epub 2017 Sep 6. PMID: 28888902.
1: Wang Y, Fan X, Xing L, Tian F. Wnt signaling: a promising target for osteoarthritis therapy. Cell Commun Signal. 2019 Aug 16;17(1):97. doi: 10.1186/s12964-019-0411-x. PMID: 31420042; PMCID: PMC6697957. 2: Moroney MR, Woodruff E, Qamar L, Bradford AP, Wolsky R, Bitler BG, Corr BR. Inhibiting Wnt/beta-catenin in CTNNB1-mutated endometrial cancer. Mol Carcinog. 2021 Aug;60(8):511-523. doi: 10.1002/mc.23308. Epub 2021 May 26. PMID: 34038589. 3: Deshmukh V, O'Green AL, Bossard C, Seo T, Lamangan L, Ibanez M, Ghias A, Lai C, Do L, Cho S, Cahiwat J, Chiu K, Pedraza M, Anderson S, Harris R, Dellamary L, Kc S, Barroga C, Melchior B, Tam B, Kennedy S, Tambiah J, Hood J, Yazici Y. Modulation of the Wnt pathway through inhibition of CLK2 and DYRK1A by lorecivivint as a novel, potentially disease-modifying approach for knee osteoarthritis treatment. Osteoarthritis Cartilage. 2019 Sep;27(9):1347-1360. doi: 10.1016/j.joca.2019.05.006. Epub 2019 May 25. PMID: 31132406. 4: Krasselt M, Baerwald C. Arthrose – neue therapeutische Ansätze [Osteoarthritis: what's new?]. Dtsch Med Wochenschr. 2022 Mar;147(6):344-348. German. doi: 10.1055/a-1612-6927. Epub 2022 Mar 15. PMID: 35291041. 5: Sabha M, Siaton BC, Hochberg MC. Lorecivivint, an intra-articular potential disease-modifying osteoarthritis drug. Expert Opin Investig Drugs. 2020 Dec;29(12):1339-1346. doi: 10.1080/13543784.2020.1842357. Epub 2020 Nov 8. PMID: 33096010. 6: De Palma A, Nalesso G. WNT Signalling in Osteoarthritis and Its Pharmacological Targeting. Handb Exp Pharmacol. 2021;269:337-356. doi: 10.1007/164_2021_525. PMID: 34510305. 7: Rodriguez-Merchan EC. The Current Role of Disease-modifying Osteoarthritis Drugs. Arch Bone Jt Surg. 2023;11(1):11-22. doi: 10.22038/ABJS.2021.56530.2807. PMID: 36793668; PMCID: PMC9903308. 8: Moreno-Londoño AP, Castañeda-Patlán MC, Sarabia-Sánchez MA, Macías-Silva M, Robles-Flores M. Canonical Wnt Pathway Is Involved in Chemoresistance and Cell Cycle Arrest Induction in Colon Cancer Cell Line Spheroids. Int J Mol Sci. 2023 Mar 9;24(6):5252. doi: 10.3390/ijms24065252. PMID: 36982333; PMCID: PMC10049556. 9: Goswami VG, Patel BD. Recent updates on Wnt signaling modulators: a patent review (2014-2020). Expert Opin Ther Pat. 2021 Nov;31(11):1009-1043. doi: 10.1080/13543776.2021.1940138. Epub 2021 Aug 18. PMID: 34128760. 10: Song M, Pang L, Zhang M, Qu Y, Laster KV, Dong Z. Cdc2-like kinases: structure, biological function, and therapeutic targets for diseases. Signal Transduct Target Ther. 2023 Apr 7;8(1):148. doi: 10.1038/s41392-023-01409-4. PMID: 37029108; PMCID: PMC10082069. 11: Lories RJ, Monteagudo S. Review Article: Is Wnt Signaling an Attractive Target for the Treatment of Osteoarthritis? Rheumatol Ther. 2020 Jun;7(2):259-270. doi: 10.1007/s40744-020-00205-8. Epub 2020 Apr 10. PMID: 32277404; PMCID: PMC7211213. 12: Cherifi C, Monteagudo S, Lories RJ. Promising targets for therapy of osteoarthritis: a review on the Wnt and TGF-β signalling pathways. Ther Adv Musculoskelet Dis. 2021 Apr 16;13:1759720X211006959. doi: 10.1177/1759720X211006959. PMID: 33948125; PMCID: PMC8053758. 13: Qin Z, Qin L, Feng X, Li Z, Bian J. Development of Cdc2-like Kinase 2 Inhibitors: Achievements and Future Directions. J Med Chem. 2021 Sep 23;64(18):13191-13211. doi: 10.1021/acs.jmedchem.1c00985. Epub 2021 Sep 14. PMID: 34519506. 14: Onuora S. Osteoarthritis: Wnt inhibitor shows potential as a DMOAD. Nat Rev Rheumatol. 2017 Nov;13(11):634. doi: 10.1038/nrrheum.2017.164. Epub 2017 Oct 5. PMID: 28978991. 15: Lane NE. INHIBITION OF WINGLESS-RELATED INTEGRATION SITE (WNT) SIGNALLING MAY TREAT OSTEOARTHRITIS OF THE KNEE. Trans Am Clin Climatol Assoc. 2020;131:55-64. PMID: 32675843; PMCID: PMC7358486. 16: Tambiah JRS, Simsek I, Swearingen CJ, Kennedy S, Cole BJ, McAlindon TE, Yazici Y. Comparing Patient-Reported Outcomes From Sham and Saline-Based Placebo Injections for Knee Osteoarthritis: Data From a Randomized Clinical Trial of Lorecivivint. Am J Sports Med. 2022 Mar;50(3):630-636. doi: 10.1177/03635465211067201. Epub 2022 Jan 10. PMID: 35005990. 17: Hua B, Qiu J, Ye X, Liu X. Intra-articular injection of a novel Wnt pathway inhibitor, SM04690, upregulates Wnt16 expression and reduces disease progression in temporomandibular joint osteoarthritis. Bone. 2022 May;158:116372. doi: 10.1016/j.bone.2022.116372. Epub 2022 Feb 23. PMID: 35218985. 18: Yazici Y, McAlindon TE, Gibofsky A, Lane NE, Lattermann C, Skrepnik N, Swearingen CJ, Simsek I, Ghandehari H, DiFrancesco A, Gibbs J, Tambiah JRS, Hochberg MC. A Phase 2b randomized trial of lorecivivint, a novel intra- articular CLK2/DYRK1A inhibitor and Wnt pathway modulator for knee osteoarthritis. Osteoarthritis Cartilage. 2021 May;29(5):654-666. doi: 10.1016/j.joca.2021.02.004. Epub 2021 Feb 12. PMID: 33588087. 19: Deshmukh V, Ibanez M, Hu H, Cahiwat J, Wei Y, Stewart J, Hood J, Yazici Y. A small-molecule inhibitor of the Wnt pathway, lorecivivint (SM04690), as a potential disease-modifying agent for the treatment of degenerative disc disease. Spine J. 2020 Sep;20(9):1492-1502. doi: 10.1016/j.spinee.2020.04.024. Epub 2020 May 12. PMID: 32413487. 20: Deshmukh V, Hu H, Barroga C, Bossard C, Kc S, Dellamary L, Stewart J, Chiu K, Ibanez M, Pedraza M, Seo T, Do L, Cho S, Cahiwat J, Tam B, Tambiah JRS, Hood J, Lane NE, Yazici Y. A small-molecule inhibitor of the Wnt pathway (SM04690) as a potential disease modifying agent for the treatment of osteoarthritis of the knee. Osteoarthritis Cartilage. 2018 Jan;26(1):18-27. doi: 10.1016/j.joca.2017.08.015. Epub 2017 Sep 6. PMID: 28888902.

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