NPASS Compound

Natural Product: NPC483450

Natural Product ID	NPC483450
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	PVCOJNPKQYNQCB-SREVYHEPSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

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 56 56 0 0 0 0 0 0 0 0999 V2000 6.2177 -2.0560 0.9498 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7616 -2.3011 0.6996 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3464 -2.0463 -0.7339 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6194 -0.6045 -1.1328 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2323 -0.3154 -2.5086 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3383 0.5778 -2.8779 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6112 1.4052 -1.9009 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1199 1.1092 -2.0814 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2428 1.8806 -1.1617 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5331 1.6010 0.2734 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3783 2.3892 1.1912 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8242 2.0833 0.9871 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1242 0.6070 1.2400 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5876 0.3558 1.0247 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4452 1.3783 0.6757 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8025 1.1055 0.4863 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3262 -0.1614 0.6360 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4596 -1.1749 0.9848 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1013 -0.9199 1.1779 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1908 -1.9910 1.5435 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9715 -2.2628 2.7279 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5285 -2.7532 0.4614 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8795 -2.4856 1.1615 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.6936 2.1196 0.1329 O 0 0 0 0 0 0 0 0 0 0 0 0 6.5957 -2.7033 1.7825 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3086 -0.9955 1.3213 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8285 -2.1609 0.0303 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1114 -1.7485 1.4134 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5845 -3.3964 0.8769 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8915 -2.7599 -1.3593 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2457 -2.1799 -0.7769 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2982 0.0919 -0.3569 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7599 -0.5368 -1.1025 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6993 -0.8642 -3.3574 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1060 0.7318 -3.9601 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8285 1.2283 -0.8594 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7243 2.4748 -2.1922 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9076 0.0322 -1.9472 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8115 1.3352 -3.1441 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8116 1.5890 -1.3821 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2931 2.9801 -1.3140 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5683 1.9904 0.5028 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5585 0.5254 0.5104 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0614 2.2431 2.2263 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2275 3.4639 0.9383 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4056 2.7216 1.6813 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1381 2.3549 -0.0381 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9317 0.4453 2.3336 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5372 -0.0450 0.5954 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0856 2.4009 0.5443 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3883 -0.3658 0.4859 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2183 -3.5167 0.0239 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2309 -2.1115 -0.4008 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6244 -3.2779 0.8498 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7534 -2.5951 1.6933 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4165 3.0600 0.4249 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 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 2 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 20 22 1 0 18 23 1 0 16 24 1 0 19 14 1 0 1 25 1 0 1 26 1 0 1 27 1 0 2 28 1 0 2 29 1 0 3 30 1 0 3 31 1 0 4 32 1 0 4 33 1 0 5 34 1 0 6 35 1 0 7 36 1 0 7 37 1 0 8 38 1 0 8 39 1 0 9 40 1 0 9 41 1 0 10 42 1 0 10 43 1 0 11 44 1 0 11 45 1 0 12 46 1 0 12 47 1 0 13 48 1 0 13 49 1 0 15 50 1 0 17 51 1 0 22 52 1 0 22 53 1 0 22 54 1 0 23 55 1 0 24 56 1 0 M END

Standard InCHIKey	PVCOJNPKQYNQCB-SREVYHEPSA-N
Standard InCHI	InChI=1S/C21H32O3/c1-3-4-5-6-7-8-9-10-11-12-13-14-18-15-19(23)16-20(24)21(18)17(2)22/h6-7,15-16,23-24H,3-5,8-14H2,1-2H3/b7-6-
SMILES	CCCC/C=CCCCCCCCc1cc(cc(c1C(=O)C)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	332.24	Volume:	376.404 ? Van der Waals volume.
Dense:	0.883	LogP:	6.723 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.047 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.919 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	12.0	Rigid Bonds:	8.0
TPSA:	57.53 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	2.0	Rings:	1.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.283	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.518	Fsp³:	0.571
MCE-18:	8.0 ? 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:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.635	Fluc inhibitor:	0.08 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.019 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.21 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.818	Promiscuous compounds:	0.074

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.131	MDCK Permeability:	-4.677
Pgp-inhibitor:	0.998	Pgp-substrate:	0.001
PAMPA:	0.0 ? 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):	0.006
20% Bioavailability (F20%):	0.489	30% Bioavailability (F30%):	0.863
50% Bioavailability (F50%):	0.935

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.139	MRP1:	0.967
Plasma Protein Binding (PPB):	98.578%	Volume Distribution (VD):	-0.073
Fu:	0.546% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.066
OATP1B3 inhibitor:	0.901	BCRP inhibitor:	0.972
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.824	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.096	CYP2C19-substrate:	0.912
CYP2C9-inhibitor:	0.999	CYP2C9-substrate:	0.775
CYP2D6-inhibitor:	0.999	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.999
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.845 ? 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):

2.962

Half-life (T1/2):

1.091

ADMET: Toxicity

hERG Blockers:	0.417	hERG Blockers (10um):	0.824
Human Hepatotoxicity (H-HT):	0.262	Drug-induced Liver Injury (DILI):	0.003
AMES Toxicity:	0.252	Rat Oral Acute Toxicity:	0.072
Maximum Recommended Daily Dose:	0.333	Skin Sensitization:	1.0
Carcinogencity:	0.063	Eye Corrosion:	0.909
Eye Irritation:	0.995	Respiratory Toxicity:	0.883
Drug-induced Neurotoxicity:	0.011	Ototoxicity:	0.128
Hematotoxicity:	0.013	Drug-induced Nephrotoxicity:	0.326
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.125
A549 Cytotoxicity:	0.962	Hek293 Cytotoxicity:	0.809
BCF:	1.639 ? 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:	5.094 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.147 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.89 ? 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
NPO40175	Knema hookeriana	Species	Myristicaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[27008174]
NPO40175	Knema hookeriana	Species	Myristicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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
Ki	2

Activity Type	# Activity
Protein-protein interaction	2

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
NPT21617	Protein-protein interaction	Induced myeloid leukemia cell differentiation protein Mcl-1/BH3-interacting domain death agonist	Homo sapiens	Ki	>	33000.0	nM	PMID[27008174]
NPT21616	Protein-protein interaction	Bcl-xL/BAK	Homo sapiens	Ki	>	23000.0	nM	PMID[27008174]

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 NPC483450 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	19108
0.1-0.2	26753
0.2-0.3	3642
0.3-0.4	249
0.4-0.5	73
0.5-0.6	25
0.6-0.7	5
0.7-0.8	0
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.975	High Similarity	NPC483449
0.8293	Intermediate Similarity	NPC473691
0.8293	Intermediate Similarity	NPC477454
0.6875	Remote Similarity	NPC259942
0.6875	Remote Similarity	NPC92624
0.6	Remote Similarity	NPC53051
0.6	Remote Similarity	NPC24404
0.6	Remote Similarity	NPC313030
0.587	Remote Similarity	NPC146798
0.587	Remote Similarity	NPC222522
0.587	Remote Similarity	NPC106396
0.587	Remote Similarity	NPC94351
0.587	Remote Similarity	NPC168303
0.5556	Remote Similarity	NPC470700
0.5556	Remote Similarity	NPC54844
0.5556	Remote Similarity	NPC39097
0.5556	Remote Similarity	NPC302681
0.5556	Remote Similarity	NPC118286
0.5556	Remote Similarity	NPC109691
0.551	Remote Similarity	NPC71002
0.551	Remote Similarity	NPC302219
0.551	Remote Similarity	NPC249828
0.5319	Remote Similarity	NPC39664
0.5306	Remote Similarity	NPC483454
0.5306	Remote Similarity	NPC162314
0.5306	Remote Similarity	NPC477453
0.52	Remote Similarity	NPC94139
0.52	Remote Similarity	NPC129373
0.52	Remote Similarity	NPC242342
0.52	Remote Similarity	NPC85479
0.52	Remote Similarity	NPC147284
0.5102	Remote Similarity	NPC232523
0.5091	Remote Similarity	NPC305603

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC483450 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4539
0.1-0.2	4464
0.2-0.3	142
0.3-0.4	4
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