NPASS Compound

Natural Product: NPC31921

Natural Product ID	NPC31921
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	AQMKARDJTJSPIX-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	20744630
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0002448] Benzenoids [CHEMONTID:0000025] Phenanthrenes and derivatives [CHEMONTID:0000223] Hydrophenanthrenes

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 48 50 0 0 0 0 0 0 0 0999 V2000 5.0061 -0.1144 0.5050 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6923 0.3612 -0.0530 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9483 1.2523 0.9176 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6444 1.6293 0.1969 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7454 0.4465 0.2866 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5255 -0.7656 -0.0869 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8227 -0.8322 -0.2434 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7289 -2.0181 -0.2973 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6126 -1.7466 0.3723 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3118 -0.6452 -0.4400 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4268 0.5190 -0.6976 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2155 0.4440 -2.0733 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0820 1.8596 -0.6378 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2119 1.9411 0.3544 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2482 0.9465 -0.1126 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6453 -0.4190 0.1450 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6406 -1.3936 -0.5341 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7728 -0.7393 1.5849 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0936 0.1387 2.4138 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5517 -2.0021 2.0987 O 0 0 0 0 0 0 0 0 0 0 0 0 5.7076 0.7139 0.7222 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4840 -0.7390 -0.2799 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8475 -0.7745 1.3743 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8406 0.8744 -1.0128 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6868 0.6436 1.8066 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5090 2.1250 1.2402 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9248 1.9235 -0.8212 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2799 2.5154 0.7923 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3740 0.4100 1.3435 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2962 -1.7706 -0.5186 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5380 -2.2426 -1.3449 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2220 -2.8699 0.1888 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1807 -2.6736 0.3298 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4092 -1.4593 1.3984 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4675 -1.1478 -1.4440 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4442 -0.2562 -2.6653 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2026 -0.0480 -2.0459 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2010 1.3927 -2.6094 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5223 2.1624 -1.6277 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3645 2.6624 -0.3827 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6816 2.9550 0.1944 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8708 1.8126 1.3789 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1739 1.0189 0.4902 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4252 1.0977 -1.1783 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6113 -1.3761 -0.0311 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2255 -2.4091 -0.4541 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6852 -1.1429 -1.6091 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7842 -2.2599 3.0663 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 1 0 6 7 2 0 6 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 11 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 16 18 1 0 18 19 2 0 18 20 1 0 7 2 1 0 16 10 1 0 11 5 1 0 1 21 1 0 1 22 1 0 1 23 1 0 2 24 1 0 3 25 1 0 3 26 1 0 4 27 1 0 4 28 1 0 5 29 1 0 7 30 1 0 8 31 1 0 8 32 1 0 9 33 1 0 9 34 1 0 10 35 1 0 12 36 1 0 12 37 1 0 12 38 1 0 13 39 1 0 13 40 1 0 14 41 1 0 14 42 1 0 15 43 1 0 15 44 1 0 17 45 1 0 17 46 1 0 17 47 1 0 20 48 1 0 M END

Standard InCHIKey	AQMKARDJTJSPIX-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C18H28O2/c1-12-5-7-14-13(11-12)6-8-15-17(14,2)9-4-10-18(15,3)16(19)20/h11-12,14-15H,4-10H2,1-3H3,(H,19,20)
SMILES	CC1CCC2C(=C1)CCC1C2(C)CCCC1(C)C(=O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	276.21	Volume:	306.522 ? Van der Waals volume.
Dense:	0.901	LogP:	3.31 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.955 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.975 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	17.0
TPSA:	37.3 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	1.0	Rings:	3.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.708	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.232	Fsp³:	0.833
MCE-18:	54.545 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.019	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.005 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.071 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.846	Promiscuous compounds:	0.018

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.874	MDCK Permeability:	-4.792
Pgp-inhibitor:	0.022	Pgp-substrate:	0.001
PAMPA:	0.501 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.002
20% Bioavailability (F20%):	0.001	30% Bioavailability (F30%):	0.002
50% Bioavailability (F50%):	0.019

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.283	MRP1:	0.991
Plasma Protein Binding (PPB):	97.526%	Volume Distribution (VD):	-0.2
Fu:	2.529% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.724
OATP1B3 inhibitor:	0.915	BCRP inhibitor:	0.001
BSEP inhibitor:	0.823

ADMET: Metabolism

CYP1A2-inhibitor:	0.358	CYP1A2-substrate:	0.001
CYP2C19-inhibitor:	0.94	CYP2C19-substrate:	0.003
CYP2C9-inhibitor:	0.925	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.492	CYP3A4-substrate:	0.014
CYP2B6-substrate:	0.998	CYP2C8-inhibitor:	0.244
HLM stability:	0.589 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

2.887

Half-life (T1/2):

1.052

ADMET: Toxicity

hERG Blockers:	0.03	hERG Blockers (10um):	0.151
Human Hepatotoxicity (H-HT):	0.506	Drug-induced Liver Injury (DILI):	0.237
AMES Toxicity:	0.09	Rat Oral Acute Toxicity:	0.206
Maximum Recommended Daily Dose:	0.593	Skin Sensitization:	0.552
Carcinogencity:	0.258	Eye Corrosion:	0.11
Eye Irritation:	0.807	Respiratory Toxicity:	0.812
Drug-induced Neurotoxicity:	0.245	Ototoxicity:	0.737
Hematotoxicity:	0.334	Drug-induced Nephrotoxicity:	0.289
Genotoxicity:	0.006	RPMI-8226 Immunitoxicity:	0.047
A549 Cytotoxicity:	0.048	Hek293 Cytotoxicity:	0.059
BCF:	1.413 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	4.222 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.545 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.733 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO8300	Apis mellifera ligustica	Species	Apidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO10256	Liquidambar orientalis	Species	Altingiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2685	Sanguis draconis	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2685	Sanguis draconis	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[HerDing]
NPO10256	Liquidambar orientalis	Species	Altingiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO8300	Apis mellifera ligustica	Species	Apidae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO2685	Sanguis draconis	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[TCMID]
NPO10256	Liquidambar orientalis	Species	Altingiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO10256	Liquidambar orientalis	Species	Altingiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO10256	Liquidambar orientalis	Species	Altingiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO10256	Liquidambar orientalis	Species	Altingiaceae	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

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

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 NPC31921 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	26344
0.1-0.2	21411
0.2-0.3	1874
0.3-0.4	105
0.4-0.5	87
0.5-0.6	29
0.6-0.7	8
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	Natural Product ID
0.68	Remote Similarity	NPC161923
0.68	Remote Similarity	NPC183503
0.68	Remote Similarity	NPC283908
0.68	Remote Similarity	NPC103958
0.68	Remote Similarity	NPC610917
0.6667	Remote Similarity	NPC165711
0.6415	Remote Similarity	NPC610334
0.6346	Remote Similarity	NPC109854
0.5849	Remote Similarity	NPC198240
0.5849	Remote Similarity	NPC237591
0.5849	Remote Similarity	NPC72343
0.5849	Remote Similarity	NPC36616
0.5849	Remote Similarity	NPC3753
0.5741	Remote Similarity	NPC59436
0.566	Remote Similarity	NPC488498
0.566	Remote Similarity	NPC61952
0.566	Remote Similarity	NPC481630
0.566	Remote Similarity	NPC603184
0.5636	Remote Similarity	NPC471159
0.5636	Remote Similarity	NPC123880
0.5636	Remote Similarity	NPC18819
0.5636	Remote Similarity	NPC46610
0.5636	Remote Similarity	NPC91369
0.5593	Remote Similarity	NPC479671
0.5536	Remote Similarity	NPC269543
0.5536	Remote Similarity	NPC247783
0.5536	Remote Similarity	NPC239098
0.5484	Remote Similarity	NPC606907
0.5455	Remote Similarity	NPC192540
0.537	Remote Similarity	NPC99154
0.5345	Remote Similarity	NPC40228
0.5312	Remote Similarity	NPC610335
0.5254	Remote Similarity	NPC232344
0.5254	Remote Similarity	NPC600691
0.5082	Remote Similarity	NPC14203
0.5082	Remote Similarity	NPC229584
0.5082	Remote Similarity	NPC477782

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC31921 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6391
0.1-0.2	2624
0.2-0.3	134
0.3-0.4	0
0.4-0.5	1
0.5-0.6	0
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
		NPD

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