Avadomide

Avadomide
Legal status
Legal status	Investigational;
Identifiers
	IUPAC name 3-(5-Amino-2-methyl-4-oxoquinazolin-3-yl)piperidine-2,6-dione;
CAS Number	1015474-32-4;
PubChem CID	24967599;
IUPHAR/BPS	10522;
DrugBank	DB14857;
ChemSpider	35521266;
UNII	28DZS29F59;
KEGG	D11132;
ChEMBL	ChEMBL3989934;
Chemical and physical data
Formula	C14H14N4O3
Molar mass	286.291 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC1=NC2=CC=CC(=C2C(=O)N1C3CCC(=O)NC3=O)N;
	InChI InChI=1S/C14H14N4O3/c1-7-16-9-4-2-3-8(15)12(9)14(21)18(7)10-5-6-11(19)17-13(10)20/h2-4,10H,5-6,15H2,1H3,(H,17,19,20); Key:RSNPAKAFCAAMBH-UHFFFAOYSA-N;

Avadomide is an experimental cereblon E3 ligase modulator, or thalidomide analog studied to see if it is effective against cancer.^[1]^[2]^[3]^[4]^[5]^[6]

References

^ Nishi, Hidemi; Gotoh, Kunihito; Tomimaru, Yoshito; Kobayashi, Shogo; Sasaki, Kazuki; Iwagami, Yoshifumi; Yamada, Daisaku; Akita, Hirofumi; Asaoka, Tadafumi; Noda, Takehiro; Takahashi, Hidenori; Tanemura, Masahiro; Doki, Yuichiro; Eguchi, Hidetoshi (October 2023). "Anti-tumor effect of avadomide in gemcitabine-resistant pancreatic ductal adenocarcinoma". Cancer Chemotherapy and Pharmacology. 92 (4): 303–314. doi:10.1007/s00280-023-04531-w. PMC 10435408. PMID 37491611.
^ Nastoupil, Loretta J.; Kuruvilla, John; Chavez, Julio C.; Bijou, Fontanet; Witzig, Thomas E.; Santoro, Armando; Flinn, Ian W.; Boccomini, Carola; Kenkre, Vaishalee P.; Corradini, Paolo; Isufi, Iris; Andorsky, David J.; Klein, Leonard M.; Greenwald, Daniel R.; Sangha, Randeep; Shen, Frank; Hagner, Patrick; Li, Yan; Dobmeyer, Juergen; Gong, Nian; Uttamsingh, Shailaja; Pourdehnad, Michael; Ribrag, Vincent (May 2022). "Phase Ib study of avadomide (CC-122) in combination with rituximab in patients with relapsed/refractory diffuse large B-cell lymphoma and follicular lymphoma". EJHaem. 3 (2): 394–405. doi:10.1002/jha2.394. PMC 9175947. PMID 35846031.
^ Heim, Christopher; Hartmann, Marcus D. (1 March 2022). "High-resolution structures of the bound effectors avadomide (CC-122) and iberdomide (CC-220) highlight advantages and limitations of the MsCI4 soaking system". Acta Crystallographica Section D Structural Biology. 78 (3): 290–298. Bibcode:2022AcCrD..78..290H. doi:10.1107/S2059798322000092. PMC 8900816. PMID 35234143.
^ Hagner, Patrick R.; Chiu, Hsiling; Chopra, Vivek S.; Colombo, Martino; Patel, Nisha; Estevez, Maria Ortiz; Waldman, Michelle F.; Loos, Remco; Towfic, Fadi; Gandhi, Anita K. (2 August 2022). "Interactome of Aiolos/Ikaros Reveals Combination Rationale of Cereblon Modulators with HDAC Inhibitors in DLBCL". Clinical Cancer Research. 28 (15): 3367–3377. doi:10.1158/1078-0432.CCR-21-3347. PMC 9662945. PMID 35583604.
^ Santiesteban, Daniela Y; Duncan, Aundrietta D; Mirza, Nadeem Q; Jacques, Vincent; DeWitt, Sheila; Iyer, Swami P. (15 November 2022). "SP-3164, a Novel Cereblon-Binding Protein Degrader, Shows Activity in Preclinical Lymphoma Models". Blood. 140 (Supplement 1): 8865–8866. doi:10.1182/blood-2022-167495. S2CID 254268049.
^ Ribrag, Vincent; Chavez, Julio C.; Boccomini, Carola; Kaplan, Jason; Chandler, Jason C.; Santoro, Armando; Corradini, Paolo; Flinn, Ian W.; Advani, Ranjana; Cassier, Philippe A.; Sangha, Randeep; Kenkre, Vaishalee P.; Isufi, Iris; Uttamsingh, Shailaja; Hagner, Patrick R.; Gandhi, Anita K.; Shen, Frank; Michelliza, Sophie; Haeske, Harald; Hege, Kristen; Pourdehnad, Michael; Kuruvilla, John (February 2022). "Phase Ib study of combinations of avadomide (CC-122), CC-223, CC-292, and rituximab in patients with relapsed/refractory diffuse large B-cell lymphoma". EJHaem. 3 (1): 139–153. doi:10.1002/jha2.375. PMC 9176062. PMID 35846221.

[1] Nishi, Hidemi; Gotoh, Kunihito; Tomimaru, Yoshito; Kobayashi, Shogo; Sasaki, Kazuki; Iwagami, Yoshifumi; Yamada, Daisaku; Akita, Hirofumi; Asaoka, Tadafumi; Noda, Takehiro; Takahashi, Hidenori; Tanemura, Masahiro; Doki, Yuichiro; Eguchi, Hidetoshi (October 2023). "Anti-tumor effect of avadomide in gemcitabine-resistant pancreatic ductal adenocarcinoma". Cancer Chemotherapy and Pharmacology. 92 (4): 303–314. doi:10.1007/s00280-023-04531-w. PMC 10435408. PMID 37491611.

[2] Nastoupil, Loretta J.; Kuruvilla, John; Chavez, Julio C.; Bijou, Fontanet; Witzig, Thomas E.; Santoro, Armando; Flinn, Ian W.; Boccomini, Carola; Kenkre, Vaishalee P.; Corradini, Paolo; Isufi, Iris; Andorsky, David J.; Klein, Leonard M.; Greenwald, Daniel R.; Sangha, Randeep; Shen, Frank; Hagner, Patrick; Li, Yan; Dobmeyer, Juergen; Gong, Nian; Uttamsingh, Shailaja; Pourdehnad, Michael; Ribrag, Vincent (May 2022). "Phase Ib study of avadomide (CC-122) in combination with rituximab in patients with relapsed/refractory diffuse large B-cell lymphoma and follicular lymphoma". EJHaem. 3 (2): 394–405. doi:10.1002/jha2.394. PMC 9175947. PMID 35846031.

[3] Heim, Christopher; Hartmann, Marcus D. (1 March 2022). "High-resolution structures of the bound effectors avadomide (CC-122) and iberdomide (CC-220) highlight advantages and limitations of the MsCI4 soaking system". Acta Crystallographica Section D Structural Biology. 78 (3): 290–298. Bibcode:2022AcCrD..78..290H. doi:10.1107/S2059798322000092. PMC 8900816. PMID 35234143.

[4] Hagner, Patrick R.; Chiu, Hsiling; Chopra, Vivek S.; Colombo, Martino; Patel, Nisha; Estevez, Maria Ortiz; Waldman, Michelle F.; Loos, Remco; Towfic, Fadi; Gandhi, Anita K. (2 August 2022). "Interactome of Aiolos/Ikaros Reveals Combination Rationale of Cereblon Modulators with HDAC Inhibitors in DLBCL". Clinical Cancer Research. 28 (15): 3367–3377. doi:10.1158/1078-0432.CCR-21-3347. PMC 9662945. PMID 35583604.

[5] Santiesteban, Daniela Y; Duncan, Aundrietta D; Mirza, Nadeem Q; Jacques, Vincent; DeWitt, Sheila; Iyer, Swami P. (15 November 2022). "SP-3164, a Novel Cereblon-Binding Protein Degrader, Shows Activity in Preclinical Lymphoma Models". Blood. 140 (Supplement 1): 8865–8866. doi:10.1182/blood-2022-167495. S2CID 254268049.

[6] Ribrag, Vincent; Chavez, Julio C.; Boccomini, Carola; Kaplan, Jason; Chandler, Jason C.; Santoro, Armando; Corradini, Paolo; Flinn, Ian W.; Advani, Ranjana; Cassier, Philippe A.; Sangha, Randeep; Kenkre, Vaishalee P.; Isufi, Iris; Uttamsingh, Shailaja; Hagner, Patrick R.; Gandhi, Anita K.; Shen, Frank; Michelliza, Sophie; Haeske, Harald; Hege, Kristen; Pourdehnad, Michael; Kuruvilla, John (February 2022). "Phase Ib study of combinations of avadomide (CC-122), CC-223, CC-292, and rituximab in patients with relapsed/refractory diffuse large B-cell lymphoma". EJHaem. 3 (1): 139–153. doi:10.1002/jha2.375. PMC 9176062. PMID 35846221.

[1]

[2]

[3]

[4]

[5]

[6]

Legal status

Legal status	Investigational
Identifiers
IUPAC name 3-(5-Amino-2-methyl-4-oxoquinazolin-3-yl)piperidine-2,6-dione
CAS Number	1015474-32-4
PubChem CID	24967599
IUPHAR/BPS	10522
DrugBank	DB14857
ChemSpider	35521266
UNII	28DZS29F59
KEGG	D11132
ChEMBL	ChEMBL3989934
Chemical and physical data
Formula	C₁₄H₁₄N₄O₃
Molar mass	286.291 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES CC1=NC2=CC=CC(=C2C(=O)N1C3CCC(=O)NC3=O)N
InChI InChI=1S/C14H14N4O3/c1-7-16-9-4-2-3-8(15)12(9)14(21)18(7)10-5-6-11(19)17-13(10)20/h2-4,10H,5-6,15H2,1H3,(H,17,19,20) Key:RSNPAKAFCAAMBH-UHFFFAOYSA-N