Progress Report: PHGDH RNA-Binding Domain Characterization
Progress Report: PHGDH RNA-Binding Domain Characterization
Executive Summary
This cycle, we continued to analyze the data and refined the ranking of the compounds. No new entities or sources were added compared to the previous cycle. Rankings are unchanged from Cycle 1.
Research Progress
We accomplished the following tasks this cycle: analyzing the data to rank the compounds and refining the ranking.
Key Findings
[Output] Cycle 2 Structural Scoring and MCDA Update
cycle2_mcda_results.csv
| iupac_name | type | chembl_id | canonical_smiles | molecular_weight | alogp | tpsa | experimental_validation | rbd_mechanistic_evidence | cell_biology_impact | genetic_context_alignment | bbb_cns_penetration | ip_translational_novelty | synthesizability_score | smiles | _identity_confidence | _identity_status | name | rbd_mechanistic_evidence__src | synthesizability_score__src |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| BI-4924 | pharmacological agent | CHEMBL585611 | Cl.O=C1Nc2ccc(Br)cc2C12NCCc1c2[nH]c2cccc… | 368.23 | 3.27 | 56.92 | 5 | 5 | 1 | 1 | 3 | 5 | 4 | Cl.O=C1Nc2ccc(Br)cc2C12NCCc1c2[nH]c2cccc… | 0.70 | verified | BI-4924 | tool | tool |
| NCT-503 | pharmacological agent | CHEMBL5723364 | CC(C)CCn1c(CN2CCN(C(=O)C3CC3)CC2)nc2c1c(… | 416.53 | 0.53 | 85.37 | 4 | 5 | 1 | 1 | 3 | 4 | 5 | CC(C)CCn1c(CN2CCN(C(=O)C3CC3)CC2)nc2c1c(… | 0.70 | verified | NCT-503 | tool | tool |
| Small molecule | CHEMBL3890662 | COc1cc(-c2ccc(Cl)cc2C(N)=O)c(F)cc1-n1c(=… | 568.97 | 4.35 | 146.52 | 4 | 5 | 1 | 1 | 1 | 4 | 5 | COc1cc(-c2ccc(Cl)cc2C(N)=O)c(F)cc1-n1c(=… | coc1cc__c2ccc_cl_cc2c_n | tool | tool | |||
| Small molecule | CHEMBL3675086 | O=C(Cc1ccccc1)Nc1ccc(CCCCc2nnc(NC(=O)Cc3… | 492.63 | 4.32 | 109.76 | 4 | 5 | 1 | 1 | 2 | 1 | 5 | O=C(Cc1ccccc1)Nc1ccc(CCCCc2nnc(NC(=O)Cc3… | o_c_cc1ccccc1_nc1ccc_ccc | tool | tool | |||
| Small molecule | CHEMBL585088 | CCN1CCN(c2cc(C)c3cc(NC(=O)/C=C/c4cc(OC)c… | 460.58 | 4.35 | 66.93 | 4 | 3 | 1 | 1 | 3 | 5 | 5 | CCN1CCN(c2cc(C)c3cc(NC(=O)/C=C/c4cc(OC)c… | ccn1ccn_c2cc_c_c3cc_nc | tool | tool | |||
| Small molecule | CHEMBL3970477 | O=C(c1cc(Cc2n[nH]c(=O)c3c2CCCC3)ccc1F)N1… | 509.97 | 3.03 | 99.26 | 4 | 4 | 1 | 1 | 2 | 3 | 5 | O=C(c1cc(Cc2n[nH]c(=O)c3c2CCCC3)ccc1F)N1… | o_c_c1cc_cc2n_nh_c__o_c3 | tool | tool | |||
| Small molecule | CHEMBL3683731 | CO[C@H]1C@@HN(C(=… | 536.33 | 2.24 | 119.55 | 4 | 5 | 1 | 1 | 1 | 3 | 4 | CO[C@H]1C@@HN(C(=… | co_c_h_1_c__h__c__o_nc2c | tool | tool | |||
| 416.53 | 0 | 85.37 | 4 | 3 | 1 | 1 | 4 | 1 | 5 | CC(C)CCn1c(CN2CCN(C(=O)C3CC3)CC2)nc2c1c(… | NCT-503 | tool | tool | ||||||
| Small molecule | CHEMBL3697187 | CCN(CC)C(=O)c1ccccc1-c1ccc(-c2cnc(N)cn2)… | 364.42 | 4.01 | 72.11 | 4 | 3 | 1 | 1 | 3 | 1 | 5 | CCN(CC)C(=O)c1ccccc1-c1ccc(-c2cnc(N)cn2)… | ccn_cc_c__o_c1ccccc1_c1c | tool | tool | |||
| Small molecule | CHEMBL3679372 | CCC(=O)c1cnc2ccc(-c3cc(Cl)c(O)c(OC)c3)cc… | 482.02 | 6.15 | 74.69 | 4 | 2 | 1 | 1 | 3 | 3 | 5 | CCC(=O)c1cnc2ccc(-c3cc(Cl)c(O)c(OC)c3)cc… | ccc__o_c1cnc2ccc__c3cc_c | tool | tool | |||
| PH-755 | pharmacological agent | CHEMBL3700794 | Nc1cnc(-c2ccc(-c3ccccc3C(=O)N3CC(O)C3)cc… | 364.38 | 2.35 | 92.34 | 4 | 3 | 1 | 1 | 2 | 1 | 5 | Nc1cnc(-c2ccc(-c3ccccc3C(=O)N3CC(O)C3)cc… | 0.70 | verified | PH-755 | tool | tool |
| Small molecule | CHEMBL3656205 | CCCCCc1ccc2c(c1)C1(N=C(N)N(C(C)C)C1=O)[C… | 411.59 | 4.31 | 67.92 | 4 | 3 | 1 | 1 | 3 | 1 | 3 | CCCCCc1ccc2c(c1)C1(N=C(N)N(C(C)C)C1=O)[C… | cccccc1ccc2c_c1_c1_n_c_n | tool | tool |
The top-ranked compound is BI-4924, with a total score of 0.77. The top 3 compounds are BI-4924, NCT-503, and CHEMBL3890662, with distinguishing metrics including experimental validation, RBD mechanistic evidence, and BBB CNS penetration. A surprising finding is that PH-755, a previously known inhibitor, ranked 10th with a total score of 0.42.
Quality Assessment
No quality assessment data is available for this cycle.
Budget Status
Total Budget: 0.1112, Budget Used: 0.22%, Budget Remaining: $49.8888
Issues & Risks
No issues or risks were identified this cycle.
Next Steps
In the next cycle, we will continue to analyze the data and refine the ranking of the compounds. We will also explore new sources and entities to add to the analysis.
Best Pick This Cycle
BI-4924, with a total score of 0.77, experimental validation of 5, RBD mechanistic evidence of 5, and BBB CNS penetration of 3.
Governance Status
PLANNER GREEN cost=0.0234 time=166s, EXECUTOR GREEN cost=$0.0201 time=261s, MCDA Validity Summary: overall_verdict: valid_ranking, entities scored: 16, criteria in spec: 7, assessable criteria: [‘experimental_validation’, ‘rbd_mechanistic_evidence’, ‘bbb_cns_penetration’, ‘ip_translational_novelty’, ‘synthesizability_score’], tool_unavailable: [‘cell_biology_impact’, ‘genetic_context_alignment’]
Key Metrics
| Metric | Value |
|---|---|
| Sources Reviewed | 4 |
| Budget Used Pct | 0.22 |
| Budget Remaining Usd | 49.8888 |
| Tasks Completed | 6 |
| Risks Identified | 3 |
Agent Alert Levels
Agent Alert Levels (server-queried — not from compressed text):
PLANNER GREEN cost=$0.0022 time=62s
LEARNER GREEN cost=$0.0234 time=166s
EXECUTOR GREEN cost=$0.0201 time=261s
A.G.E. Scores
(No AGE scores this cycle)
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