NPASS Compound

Natural Product: NPC208208

Natural Product ID	NPC208208
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	JSHDAORXSNJOBA-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	16832
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0003909] Fatty Acyls [CHEMONTID:0000324] Fatty acid esters

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 29 28 0 0 0 0 0 0 0 0999 V2000 -3.7189 0.8455 -0.6898 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6836 0.0063 0.5660 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2400 -0.3927 0.8975 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6309 -1.1878 -0.2049 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2281 -1.6022 0.0976 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7052 -0.5102 0.3362 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5345 0.4504 1.1612 O 0 0 0 0 0 0 0 0 0 0 0 0 1.9114 -0.4375 -0.3606 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8402 0.6115 -0.1502 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1013 1.3902 -1.4203 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1476 -0.0539 0.2464 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6562 1.1179 -0.9417 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0854 0.2842 -1.5780 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2502 1.8003 -0.5505 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2952 -0.8990 0.4823 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0486 0.6310 1.3974 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1894 -0.9106 1.8663 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7070 0.6025 0.9384 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6106 -0.6128 -1.1756 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2298 -2.0939 -0.4519 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2370 -2.3204 0.9758 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1747 -2.2215 -0.7371 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5057 1.3241 0.6154 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1730 1.3536 -1.7056 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8602 2.4591 -1.2852 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5148 0.9865 -2.2831 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2555 -1.0177 -0.3046 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9625 0.6087 -0.0452 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1244 -0.2117 1.3247 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 9 11 1 0 1 12 1 0 1 13 1 0 1 14 1 0 2 15 1 0 2 16 1 0 3 17 1 0 3 18 1 0 4 19 1 0 4 20 1 0 5 21 1 0 5 22 1 0 9 23 1 0 10 24 1 0 10 25 1 0 10 26 1 0 11 27 1 0 11 28 1 0 11 29 1 0 M END

Standard InCHIKey	JSHDAORXSNJOBA-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C9H18O2/c1-4-5-6-7-9(10)11-8(2)3/h8H,4-7H2,1-3H3
SMILES	CCCCCC(=O)OC(C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	158.13	Volume:	179.164 ? Van der Waals volume.
Dense:	0.883	LogP:	3.15 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.722 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.665 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	1.0
TPSA:	26.3 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	0.0	Rings:	0.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.454	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	1.711	Fsp³:	0.889
MCE-18:	0.0 ? 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:	Rejected
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.022	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:	0.002 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.999	Promiscuous compounds:	0.025

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.737	MDCK Permeability:	-4.657
Pgp-inhibitor:	0.47	Pgp-substrate:	0.11
PAMPA:	0.043 ? 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):	0.007
20% Bioavailability (F20%):	0.064	30% Bioavailability (F30%):	0.292
50% Bioavailability (F50%):	0.619

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.925	MRP1:	0.984
Plasma Protein Binding (PPB):	51.518%	Volume Distribution (VD):	0.141
Fu:	45.982% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.016
OATP1B3 inhibitor:	0.529	BCRP inhibitor:	0.807
BSEP inhibitor:	0.995

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.996
CYP2C19-inhibitor:	0.62	CYP2C19-substrate:	0.997
CYP2C9-inhibitor:	0.002	CYP2C9-substrate:	0.021
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.097
CYP3A4-inhibitor:	0.06	CYP3A4-substrate:	0.627
CYP2B6-substrate:	0.335	CYP2C8-inhibitor:	0.938
HLM stability:	0.963 ? 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):

7.182

Half-life (T1/2):

0.411

ADMET: Toxicity

hERG Blockers:	0.1	hERG Blockers (10um):	0.587
Human Hepatotoxicity (H-HT):	0.364	Drug-induced Liver Injury (DILI):	0.239
AMES Toxicity:	0.12	Rat Oral Acute Toxicity:	0.151
Maximum Recommended Daily Dose:	0.134	Skin Sensitization:	0.896
Carcinogencity:	0.475	Eye Corrosion:	0.994
Eye Irritation:	0.995	Respiratory Toxicity:	0.596
Drug-induced Neurotoxicity:	0.296	Ototoxicity:	0.277
Hematotoxicity:	0.295	Drug-induced Nephrotoxicity:	0.455
Genotoxicity:	0.001	RPMI-8226 Immunitoxicity:	0.054
A549 Cytotoxicity:	0.042	Hek293 Cytotoxicity:	0.062
BCF:	0.863 ? 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:	3.025 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.264 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.076 ? 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
NPO11438	Angelica gigas	Species	Apiaceae	Eukaryota	n.a.	root	n.a.	PMID[11374978]
NPO11438	Angelica gigas	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15679317]
NPO15462	Angelica sinensis	Species	Apiaceae	Eukaryota	roots	purchased from Kiu Shun Trading Ltd., Vancouver, Canada	2000	PMID[16643021]
NPO11438	Angelica gigas	Species	Apiaceae	Eukaryota	n.a.	root	n.a.	PMID[17997069]
NPO15462	Angelica sinensis	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[25538068]
NPO15462	Angelica sinensis	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[27400088]
NPO15462	Angelica sinensis	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[36838931]
NPO15462	Angelica sinensis	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[37480748]
NPO15462	Angelica sinensis	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11438	Angelica gigas	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2921	Angelica acutiloba	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO15462	Angelica sinensis	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO2921	Angelica acutiloba	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO11438	Angelica gigas	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO11438	Angelica gigas	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO2921	Angelica acutiloba	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO15462	Angelica sinensis	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO11438	Angelica gigas	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO2921	Angelica acutiloba	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO15462	Angelica sinensis	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO11438	Angelica gigas	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO15462	Angelica sinensis	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO2921	Angelica acutiloba	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO15462	Angelica sinensis	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2921	Angelica acutiloba	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11438	Angelica gigas	Species	Apiaceae	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 NPC208208 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	25172
0.1-0.2	21771
0.2-0.3	2569
0.3-0.4	259
0.4-0.5	50
0.5-0.6	14
0.6-0.7	15
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
0.95	High Similarity	NPC47363
0.95	High Similarity	NPC287231
0.7083	Intermediate Similarity	NPC603863
0.6522	Remote Similarity	NPC105329
0.6522	Remote Similarity	NPC273545
0.6364	Remote Similarity	NPC176500
0.6296	Remote Similarity	NPC23155
0.625	Remote Similarity	NPC326957
0.625	Remote Similarity	NPC63182
0.625	Remote Similarity	NPC145045
0.625	Remote Similarity	NPC52700
0.6087	Remote Similarity	NPC201622
0.6087	Remote Similarity	NPC305660
0.6087	Remote Similarity	NPC12156
0.6087	Remote Similarity	NPC161097
0.6087	Remote Similarity	NPC28598
0.6087	Remote Similarity	NPC22903
0.6087	Remote Similarity	NPC54980
0.5909	Remote Similarity	NPC94368
0.5862	Remote Similarity	NPC55678
0.5714	Remote Similarity	NPC321699
0.5714	Remote Similarity	NPC314084
0.56	Remote Similarity	NPC250028
0.56	Remote Similarity	NPC236579
0.56	Remote Similarity	NPC80234
0.56	Remote Similarity	NPC203531
0.56	Remote Similarity	NPC256163
0.56	Remote Similarity	NPC40597
0.56	Remote Similarity	NPC317128
0.5333	Remote Similarity	NPC489810
0.5217	Remote Similarity	NPC476548
0.5152	Remote Similarity	NPC148192

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC208208 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6789
0.1-0.2	2197
0.2-0.3	144
0.3-0.4	16
0.4-0.5	1
0.5-0.6	2
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	1

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.95	High Similarity	NPD2699	Pre-clinical
0.5862	Remote Similarity	NPD6125	Phase 4
0.5152	Remote Similarity	NPD3730	Pre-clinical

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