NPASS Compound

Natural Product: NPC484730

Natural Product ID	NPC484730
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	ZTIHTXHZJDUOIZ-CBDDKAGISA-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 57 0 0 0 0 0 0 0 0999 V2000 0.3613 -2.3993 -1.5979 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3572 -1.3473 -1.3903 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6989 -1.2023 -2.0486 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7401 -0.9179 -0.9686 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2264 0.0437 0.0422 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.2486 0.5235 1.0188 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7339 -0.4769 1.9921 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4379 1.0006 0.1662 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7227 1.7735 1.6910 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2243 1.8160 1.8047 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6138 0.4379 1.9007 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9151 -0.3797 0.6892 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.9306 -1.8278 1.1195 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0887 -0.2950 -0.4303 C 0 0 1 0 0 0 0 0 0 0 0 0 1.5029 -0.1428 -0.1555 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2605 0.2953 -1.3846 C 0 0 1 0 0 0 0 0 0 0 0 0 3.7148 0.4355 -1.1260 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2311 0.1757 0.0620 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6991 0.3129 0.3394 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8349 1.2615 1.3598 O 0 0 0 0 0 0 0 0 0 0 0 0 4.6200 0.8727 -2.2195 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0064 -0.5112 -2.4544 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0457 -3.1802 -2.2753 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3246 -2.6645 -1.1828 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9150 -2.1163 -2.6124 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7328 -0.3562 -2.7481 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6248 -0.4012 -1.4521 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1769 -1.8513 -0.5584 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9898 0.9790 -0.5684 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8518 -0.4562 2.0351 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4727 -1.5266 1.7566 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4246 -0.1888 3.0376 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0473 1.4744 -0.7659 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1278 0.1730 -0.0432 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9611 1.7784 0.7589 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1906 1.8334 2.7038 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0343 2.6974 1.1610 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7290 2.3372 0.9640 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9576 2.3671 2.7292 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0432 -0.1107 2.7999 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4462 0.5578 2.1603 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6110 -2.4718 0.5737 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0945 -2.2928 1.0055 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1562 -1.9469 2.2074 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2811 0.6727 -0.9975 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7468 0.5425 0.6997 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9986 -1.1147 0.1660 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8420 1.3246 -1.7030 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6331 -0.1480 0.8926 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2004 0.7329 -0.5598 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1545 -0.6199 0.6675 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9701 1.6578 1.6155 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4373 0.1343 -2.3549 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0826 1.8637 -2.0222 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0633 0.8931 -3.1857 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9088 -0.0221 -3.3147 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 6 8 1 0 6 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 1 12 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 1 0 17 21 1 0 16 22 1 0 14 2 1 0 12 5 1 0 1 23 1 0 1 24 1 0 3 25 1 0 3 26 1 0 4 27 1 0 4 28 1 0 5 29 1 6 7 30 1 0 7 31 1 0 7 32 1 0 8 33 1 0 8 34 1 0 8 35 1 0 9 36 1 0 9 37 1 0 10 38 1 0 10 39 1 0 11 40 1 0 11 41 1 0 13 42 1 0 13 43 1 0 13 44 1 0 14 45 1 6 15 46 1 0 15 47 1 0 16 48 1 6 18 49 1 0 19 50 1 0 19 51 1 0 20 52 1 0 21 53 1 0 21 54 1 0 21 55 1 0 22 56 1 0 M END

Standard InCHIKey	ZTIHTXHZJDUOIZ-CBDDKAGISA-N
Standard InCHI	InChI=1S/C20H34O2/c1-14-7-8-18-19(3,4)10-6-11-20(18,5)16(14)13-17(22)15(2)9-12-21/h9,16-18,21-22H,1,6-8,10-13H2,2-5H3/b15-9+/t16-,17-,18-,20+/m0/s1
SMILES	C=C1CC[C@H]2C(C)(C)CCC[C@]2(C)[C@H]1C[C@@H](/C(=C/CO)/C)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	306.26	Volume:	349.671 ? Van der Waals volume.
Dense:	0.876	LogP:	3.569 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.502 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.976 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	13.0
TPSA:	40.46 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	2.0	Rings:	2.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.752	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.372	Fsp³:	0.8
MCE-18:	42.5 ? 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:	0.147	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.002 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.835	Promiscuous compounds:	0.244

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.705	MDCK Permeability:	-4.859
Pgp-inhibitor:	0.032	Pgp-substrate:	0.0
PAMPA:	0.094 ? 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):	0.042
20% Bioavailability (F20%):	0.74	30% Bioavailability (F30%):	0.978
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.008	MRP1:	0.153
Plasma Protein Binding (PPB):	95.515%	Volume Distribution (VD):	0.294
Fu:	5.389% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.406
BSEP inhibitor:	0.089

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.913	CYP2C19-substrate:	0.007
CYP2C9-inhibitor:	0.01	CYP2C9-substrate:	0.042
CYP2D6-inhibitor:	0.985	CYP2D6-substrate:	0.107
CYP3A4-inhibitor:	0.038	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.001
HLM stability:	0.77 ? 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):

11.717

Half-life (T1/2):

0.985

ADMET: Toxicity

hERG Blockers:	0.054	hERG Blockers (10um):	0.333
Human Hepatotoxicity (H-HT):	0.659	Drug-induced Liver Injury (DILI):	0.316
AMES Toxicity:	0.398	Rat Oral Acute Toxicity:	0.318
Maximum Recommended Daily Dose:	0.511	Skin Sensitization:	0.989
Carcinogencity:	0.798	Eye Corrosion:	0.101
Eye Irritation:	0.874	Respiratory Toxicity:	0.775
Drug-induced Neurotoxicity:	0.539	Ototoxicity:	0.492
Hematotoxicity:	0.489	Drug-induced Nephrotoxicity:	0.766
Genotoxicity:	0.126	RPMI-8226 Immunitoxicity:	0.094
A549 Cytotoxicity:	0.396	Hek293 Cytotoxicity:	0.436
BCF:	2.27 ? 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:	4.634 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.039 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.495 ? 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
NPO7052	Physalis nicandroides	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[25634541]
NPO7052	Physalis nicandroides	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[31429569]
NPO7052	Physalis nicandroides	Species	Solanaceae	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
Activity	2

Activity Type	# Activity
Individual protein	1
Others	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT66	Individual protein	Acetylcholinesterase	Electrophorus electricus	Activity	=	6.7	%	PMID[31429569]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT2	Others	Unspecified	n.a.	Activity	=	1.1	%	PMID[31429569]

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 NPC484730 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	23703
0.1-0.2	22987
0.2-0.3	2711
0.3-0.4	357
0.4-0.5	71
0.5-0.6	12
0.6-0.7	14
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC484729
0.6957	Remote Similarity	NPC306727
0.6739	Remote Similarity	NPC226997
0.6596	Remote Similarity	NPC68703
0.6458	Remote Similarity	NPC34834
0.62	Remote Similarity	NPC484731
0.62	Remote Similarity	NPC189745
0.6122	Remote Similarity	NPC251155
0.6122	Remote Similarity	NPC479672
0.6111	Remote Similarity	NPC311070
0.6111	Remote Similarity	NPC472809
0.6111	Remote Similarity	NPC177037
0.6111	Remote Similarity	NPC472810
0.6111	Remote Similarity	NPC475709
0.6111	Remote Similarity	NPC472814
0.5833	Remote Similarity	NPC41160
0.5833	Remote Similarity	NPC67840
0.5789	Remote Similarity	NPC489288
0.566	Remote Similarity	NPC99321
0.5577	Remote Similarity	NPC175334
0.54	Remote Similarity	NPC143765
0.5294	Remote Similarity	NPC69649
0.5238	Remote Similarity	NPC484733
0.5172	Remote Similarity	NPC470711
0.5172	Remote Similarity	NPC470758
0.5116	Remote Similarity	NPC103290
0.5088	Remote Similarity	NPC79027

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC484730 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7732
0.1-0.2	1338
0.2-0.3	59
0.3-0.4	20
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