NPASS Compound

Natural Product: NPC126940

Natural Product ID	NPC126940
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	NVECILAMICWAEO-VYJAJWGXSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	11267184
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000368] Dioxanes [CHEMONTID:0001312] 1,2-dioxanes

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 55 58 0 0 0 0 0 0 0 0999 V2000 4.9607 1.3121 0.8440 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4085 -0.0950 0.9092 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2375 -0.9745 0.0380 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0107 -0.0738 0.4045 C 0 0 2 0 0 0 0 0 0 0 0 0 2.8819 0.4079 -1.0223 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4171 0.5427 -1.3586 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6219 -0.1568 -0.2831 C 0 0 1 0 0 0 0 0 0 0 0 0 0.8408 0.6947 0.9124 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0990 0.7292 1.3105 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2224 1.4414 1.5984 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4724 1.5416 0.7298 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7770 0.0999 0.3219 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.2209 -0.0822 0.0007 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.8174 1.0564 -0.7984 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4835 -1.4165 -0.6140 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3908 -2.4057 -0.4487 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0196 -1.9564 -0.6837 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7925 -0.4395 -0.6408 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.9854 0.0226 -2.0688 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9652 -0.0596 1.3528 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3226 -0.2393 0.9867 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2612 -1.3986 -0.1010 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4287 -1.3493 0.4231 O 0 0 0 0 0 0 0 0 0 0 0 0 5.8056 1.3525 1.5712 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1644 1.9973 1.1925 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3153 1.5509 -0.1670 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4144 -0.4902 1.9266 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8555 -2.0157 -0.0171 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2881 -1.0586 0.4269 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3423 -0.6069 -1.0020 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2924 -0.3870 -1.7107 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4274 1.3626 -1.1842 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2058 1.6531 -1.3605 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2381 0.2039 -2.3745 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5030 1.2413 2.1615 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5230 0.9392 2.5577 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0479 2.4744 1.8743 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3259 2.2109 -0.1254 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2697 1.9218 1.3570 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6125 -0.4828 1.2809 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5590 1.6436 -0.2183 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0427 1.7860 -1.1089 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3804 0.6819 -1.6899 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8459 -1.3433 -1.6857 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4000 -1.8856 -0.1311 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6102 -3.2585 -1.1594 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5131 -2.8890 0.5661 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3686 -2.3646 0.1452 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5419 -2.3572 -1.6233 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5957 1.0461 -2.2220 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5113 -0.7524 -2.7082 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0452 0.0352 -2.3963 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6944 -0.9180 1.9693 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9348 0.9130 1.8388 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8242 0.5948 0.9897 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 4 2 1 1 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 2 0 8 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 6 13 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 6 13 20 1 0 20 21 1 0 7 22 1 1 22 23 1 0 9 4 1 0 18 12 1 0 23 4 1 0 18 7 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 3 30 1 0 5 31 1 0 5 32 1 0 6 33 1 0 6 34 1 0 9 35 1 0 10 36 1 0 10 37 1 0 11 38 1 0 11 39 1 0 12 40 1 1 14 41 1 0 14 42 1 0 14 43 1 0 15 44 1 0 15 45 1 0 16 46 1 0 16 47 1 0 17 48 1 0 17 49 1 0 19 50 1 0 19 51 1 0 19 52 1 0 20 53 1 0 20 54 1 0 21 55 1 0 M END

Standard InCHIKey	NVECILAMICWAEO-VYJAJWGXSA-N
Standard InCHI	InChI=1S/C20H32O3/c1-14(2)19-10-11-20(23-22-19)15(12-19)6-7-16-17(3,13-21)8-5-9-18(16,20)4/h12,14,16,21H,5-11,13H2,1-4H3/t16-,17-,18-,19-,20+/m0/s1
SMILES	CC(C)[C@]12CC[C@]3(C(=C1)CC[C@H]1[C@@](C)(CCC[C@]31C)CO)OO2

Calculated Properties

Physi-Chem Properties

Molecular Weight:	320.24	Volume:	343.985 ? Van der Waals volume.
Dense:	0.931	LogP:	2.997 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.079 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.864 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	19.0
TPSA:	38.69 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	1.0	Rings:	5.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.605	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	6.2	Fsp³:	0.9
MCE-18:	98.053 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.081	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.003 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.015 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.456	Promiscuous compounds:	0.227

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.714	MDCK Permeability:	-4.692
Pgp-inhibitor:	0.788	Pgp-substrate:	0.032
PAMPA:	0.022 ? 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):	0.0
20% Bioavailability (F20%):	0.309	30% Bioavailability (F30%):	0.371
50% Bioavailability (F50%):	0.975

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.946	MRP1:	0.773
Plasma Protein Binding (PPB):	95.337%	Volume Distribution (VD):	0.488
Fu:	5.264% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.977	BCRP inhibitor:	0.456
BSEP inhibitor:	0.953

ADMET: Metabolism

CYP1A2-inhibitor:	0.743	CYP1A2-substrate:	0.012
CYP2C19-inhibitor:	0.998	CYP2C19-substrate:	0.009
CYP2C9-inhibitor:	0.074	CYP2C9-substrate:	0.499
CYP2D6-inhibitor:	0.784	CYP2D6-substrate:	0.328
CYP3A4-inhibitor:	0.999	CYP3A4-substrate:	0.986
CYP2B6-substrate:	0.166	CYP2C8-inhibitor:	0.388
HLM stability:	0.958 ? 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):

13.079

Half-life (T1/2):

0.974

ADMET: Toxicity

hERG Blockers:	0.577	hERG Blockers (10um):	0.786
Human Hepatotoxicity (H-HT):	0.72	Drug-induced Liver Injury (DILI):	0.202
AMES Toxicity:	0.428	Rat Oral Acute Toxicity:	0.811
Maximum Recommended Daily Dose:	0.918	Skin Sensitization:	0.979
Carcinogencity:	0.864	Eye Corrosion:	0.0
Eye Irritation:	0.081	Respiratory Toxicity:	0.53
Drug-induced Neurotoxicity:	0.455	Ototoxicity:	0.495
Hematotoxicity:	0.078	Drug-induced Nephrotoxicity:	0.154
Genotoxicity:	0.896	RPMI-8226 Immunitoxicity:	0.129
A549 Cytotoxicity:	0.197	Hek293 Cytotoxicity:	0.645
BCF:	2.114 ? 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:	4.012 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.276 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.73 ? 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
NPO21179	Streptomyces griseoaurantiacus	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	PMID[10048567]
NPO21179	Streptomyces griseoaurantiacus	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13308	Polycitor adriaticus	Species	Polycitoridae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO18881	Loropetalum chinense	Species	Hamamelidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO22530	Vigna luteola	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14307	Rhizopus oryzae	Species	Rhizopodaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO18881	Loropetalum chinense	Species	Hamamelidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO14307	Rhizopus oryzae	Species	Rhizopodaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO18881	Loropetalum chinense	Species	Hamamelidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO18881	Loropetalum chinense	Species	Hamamelidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO13308	Polycitor adriaticus	Species	Polycitoridae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22530	Vigna luteola	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21179	Streptomyces griseoaurantiacus	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]
NPO18881	Loropetalum chinense	Species	Hamamelidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO14307	Rhizopus oryzae	Species	Rhizopodaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23157	Wigandia kunthii	Species	Namaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21704	Papaver suaveolens	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23194	Berberis beaniana	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20425	Epimedium macranthum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6953.1	Aconitum sachalinense subsp. yezoense	Subspecies	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO15469	Myodocarpus gracilis	Species	Myodocarpaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22968	Elaeocarpus serratus	Species	Elaeocarpaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21894	Psychotria granadensis	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22147	Goniothalamus macrophyllus	Species	Annonaceae	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 NPC126940 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	20632
0.1-0.2	27145
0.2-0.3	1995
0.3-0.4	79
0.4-0.5	1
0.5-0.6	5
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	Natural Product ID
0.7143	Intermediate Similarity	NPC481009
0.7143	Intermediate Similarity	NPC481010
0.5312	Remote Similarity	NPC476417
0.5263	Remote Similarity	NPC475101
0.5263	Remote Similarity	NPC124927
0.5263	Remote Similarity	NPC481008
0.5263	Remote Similarity	NPC476427

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC126940 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7150
0.1-0.2	1945
0.2-0.3	55
0.3-0.4	0
0.4-0.5	0
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