Synonym
AOH1996; AOH-1996; AOH 1996; NSC789796; NSC 789796; NSC-789796;
IUPAC/Chemical Name
N-[2-[2-(3-methoxyphenoxy)anilino]-2-oxoethyl]naphthalene-1-carboxamide
InChi Key
HDMONPHKMIZXDH-UHFFFAOYSA-N
InChi Code
1S/C26H22N2O4/c1-31-19-10-7-11-20(16-19)32-24-15-5-4-14-23(24)28-25(29)17-27-26(30)22-13-6-9-18-8-2-3-12-21(18)22/h2-16H,17H2,1H3,(H,27,30)(H,28,29)
SMILES Code
O=C(C1=C2C=CC=CC2=CC=C1)NCC(NC3=CC=CC=C3OC4=CC=CC(OC)=C4)=O
Appearance
To be determined
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
To be determined
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
Targeting transcription replication conflicts, a major source of endogenous DNA double-stranded breaks and genomic instability could have important anticancer therapeutic implications. Proliferating cell nuclear antigen (PCNA) is critical to DNA replication and repair processes.
AOH1996 is an experimental anticancer medication which acts as a small molecule inhibitor of proliferating cell nuclear antigen (PCNA) and as of August 2023 is in Phase I clinical trials for the treatment of solid tumors.
It was created to target a specific variant of PCNA found only in cancer cells. This protein is crucial in the body for DNA repair, but targeting it was difficult because of its role in healthy cells. By going after only the variant, it may be possible to selectively target only cancer cells.[5] In vitro testing has suggested that it is effective against a range of cancers including breast, prostate, brain, ovarian, cervical, skin and lung cancers.[6]
The substance has been named after the initials and the birth year of Anna Olivia Healey, who died of neuroblastoma in 2006. The funds collected by her parents have helped support the development of the chemical compound.
Source: https://en.wikipedia.org/wiki/AOH1996
Biological target:
AOH1996 boosts PCNA-RPB1 interaction, detaching PCNA from active chromatin, and causing transcription-dependent DNA double-stranded breaks. A point mutation in RPB1's PCNA-binding region grants resistance to AOH1996.
In vitro activity:
This study discovered AOH1996, a selective cancer cell killer. AOH1996 boosts the interaction between PCNA and RPB1, disrupting PCNA's presence in actively transcribed chromatin regions. It induces DNA double-stranded breaks in a transcription-dependent manner. A point mutation in RPB1's PCNA-binding region makes cells resistant to AOH1996. AOH1996, administered orally and metabolically stable, effectively suppresses tumor growth alone or in combination therapy without causing noticeable side effects.
Reference: Cell Chem Biol. 2023 Jul 26:S2451-9456(23)00221-0. https://pubmed.ncbi.nlm.nih.gov/37531956/
In vivo activity:
To be determined in the future
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
125.0 |
293.11 |
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
426.47
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. Gu L, Li M, Li CM, Haratipour P, Lingeman R, Jossart J, Gutova M, Flores L, Hyde C, Kenjić N, Li H, Chung V, Li H, Lomenick B, Von Hoff DD, Synold TW, Aboody KS, Liu Y, Horne D, Hickey RJ, Perry JJP, Malkas LH. Small molecule targeting of transcription-replication conflict for selective chemotherapy. Cell Chem Biol. 2023 Jul 26:S2451-9456(23)00221-0. doi: 10.1016/j.chembiol.2023.07.001. Epub ahead of print. PMID: 37531956.
In vitro protocol:
1. Gu L, Li M, Li CM, Haratipour P, Lingeman R, Jossart J, Gutova M, Flores L, Hyde C, Kenjić N, Li H, Chung V, Li H, Lomenick B, Von Hoff DD, Synold TW, Aboody KS, Liu Y, Horne D, Hickey RJ, Perry JJP, Malkas LH. Small molecule targeting of transcription-replication conflict for selective chemotherapy. Cell Chem Biol. 2023 Jul 26:S2451-9456(23)00221-0. doi: 10.1016/j.chembiol.2023.07.001. Epub ahead of print. PMID: 37531956.
In vivo protocol:
To be determined
Gu L, Li M, Li CM, Haratipour P, Lingeman R, Jossart J, Gutova M, Flores L, Hyde C, Kenjić N, Li H, Chung V, Li H, Lomenick B, Von Hoff DD, Synold TW, Aboody KS, Liu Y, Horne D, Hickey RJ, Perry JJP, Malkas LH. Small molecule targeting of transcription-replication conflict for selective chemotherapy. Cell Chem Biol. 2023 Jul 26:S2451-9456(23)00221-0. doi: 10.1016/j.chembiol.2023.07.001. Epub ahead of print. PMID: 37531956.
