NPASS Compound

Natural Product: NPC228835

Natural Product ID	NPC228835
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	3(S)-(1H-Indol-3-Ylmethyl)-6-(R)-Isobutyl-1-Methylpiperazine-2,5-Dione
IUPAC Name	(3S,6R)-3-(1H-indol-3-ylmethyl)-1-methyl-6-(2-methylpropyl)piperazine-2,5-dione
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL469410
PubChem CID	11529722
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0000265] Carboxylic acids and derivatives [CHEMONTID:0000013] Amino acids, peptides, and analogues [CHEMONTID:0000347] Amino acids and derivatives [CHEMONTID:0000060] Alpha amino acids and derivatives

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 46 48 0 0 0 0 0 0 0 0999 V2000 -4.8274 -1.5379 0.4483 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4456 -0.8661 0.5040 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7131 -1.3267 -0.7074 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3301 -0.8088 -0.8795 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.4276 -1.1678 0.2400 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1376 -0.2959 1.0047 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.0053 1.1168 0.9061 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.6870 1.5594 -0.3233 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7989 2.7683 -0.6171 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2282 0.5855 -1.1919 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.7115 1.0355 -2.5009 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2697 1.8243 1.1838 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3927 1.4854 0.2807 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8180 2.2357 -0.8094 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8498 1.6150 -1.4099 N 0 0 0 0 0 0 0 0 0 0 0 0 4.1261 0.4735 -0.7534 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2271 0.3921 0.2914 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3259 -0.7042 1.1142 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2725 -1.6976 0.9275 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1463 -1.5760 -0.1255 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0854 -0.4940 -0.9761 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1641 -2.5058 0.4953 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7093 0.5982 0.5886 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1478 -1.6483 -0.5990 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5735 -0.9048 0.9664 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8032 -2.5175 0.9856 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9543 -1.2802 1.4086 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3419 -1.1240 -1.5989 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6411 -2.4465 -0.6514 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9023 -1.3497 -1.7778 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7067 1.4108 1.7470 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8933 1.0768 -3.2482 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1768 2.0372 -2.3349 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5131 0.3649 -2.8736 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1159 2.9434 1.2280 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5536 1.5724 2.2497 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4098 3.1700 -1.1485 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3609 1.9577 -2.2523 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6621 -0.8193 1.9470 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3144 -2.5420 1.5983 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9032 -2.3412 -0.3002 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7990 -0.4568 -1.7831 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4474 -2.7840 1.2787 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7483 0.8147 0.9824 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7214 1.0209 -0.4314 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0455 1.1366 1.2951 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 1 0 8 9 2 0 8 10 1 0 10 11 1 0 7 12 1 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 2 0 5 22 1 0 2 23 1 0 10 4 1 0 17 13 1 0 21 16 1 0 1 24 1 0 1 25 1 0 1 26 1 0 2 27 1 0 3 28 1 0 3 29 1 0 4 30 1 6 7 31 1 1 11 32 1 0 11 33 1 0 11 34 1 0 12 35 1 0 12 36 1 0 14 37 1 0 15 38 1 0 18 39 1 0 19 40 1 0 20 41 1 0 21 42 1 0 22 43 1 0 23 44 1 0 23 45 1 0 23 46 1 0 M END

Standard InCHIKey	ZXMLGZPFSBKFTE-JKSUJKDBSA-N
Standard InCHI	InChI=1S/C18H23N3O2/c1-11(2)8-16-17(22)20-15(18(23)21(16)3)9-12-10-19-14-7-5-4-6-13(12)14/h4-7,10-11,15-16,19H,8-9H2,1-3H3,(H,20,22)/t15-,16+/m0/s1
SMILES	CC(C[C@@H]1C(=N[C@H](C(=O)N1C)Cc1c[nH]c2c1cccc2)O)C

Calculated Properties

Physi-Chem Properties

MedChem Properties

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

ADMET: Distribution

ADMET: Metabolism

ADMET: Excretion

ADMET: Toxicity

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO23756	Aspergillus flavus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16124785]
NPO33480	leptoxyphium sp.	Species	Capnodiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19637889]
NPO23756	Aspergillus flavus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24738739]
NPO23756	Aspergillus flavus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[31050424]
NPO23756	Aspergillus flavus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[4207788]
NPO23756	Aspergillus flavus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[4629903]
NPO23756	Aspergillus flavus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[7528269]
NPO23756	Aspergillus flavus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO23756	Aspergillus flavus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	Organism Name	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
IC50	2

Activity Type	# Activity
Cell line	1
Organism	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT404	Cell line	CCRF-CEM	Homo sapiens	IC50	>	31000.0	nM	PMID[23999041]
NPT20	Organism	Candida albicans	Candida albicans	IC50	>	31000.0	nM	PMID[20350944]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC228835 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	26134
0.1-0.2	21754
0.2-0.3	1474
0.3-0.4	341
0.4-0.5	136
0.5-0.6	11
0.6-0.7	1
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8103	Intermediate Similarity	NPC11126
0.7344	Intermediate Similarity	NPC17059
0.6173	Remote Similarity	NPC487596
0.5909	Remote Similarity	NPC49954
0.5833	Remote Similarity	NPC59269
0.5783	Remote Similarity	NPC489625
0.5625	Remote Similarity	NPC282231
0.5385	Remote Similarity	NPC480549
0.5373	Remote Similarity	NPC480548
0.5224	Remote Similarity	NPC63751
0.5224	Remote Similarity	NPC279918
0.5147	Remote Similarity	NPC54988
0.5106	Remote Similarity	NPC54420
0.5057	Remote Similarity	NPC213629

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC228835 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3051
0.1-0.2	5779
0.2-0.3	247
0.3-0.4	52
0.4-0.5	17
0.5-0.6	3
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.5541	Remote Similarity	NPD4184	Phase 2
0.5287	Remote Similarity	NPD7619	Phase 3
0.5227	Remote Similarity	NPD7618	Phase 3

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data