NPASS Compound

Natural Product: NPC258567

Natural Product ID	NPC258567
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	5's-Hydroxyumbelliprenin
IUPAC Name	7-[(2E,5S,6E)-5-hydroxy-3,7,11-trimethyldodeca-2,6,10-trienoxy]chromen-2-one
Synonyms	5'S-Hydroxyumbelliprenin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1079137
PubChem CID	44631968
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001283] Terpene lactones

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 58 59 0 0 0 0 0 0 0 0999 V2000 1.6440 0.0746 0.0650 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3179 -0.2559 -1.3288 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2645 -0.5456 -2.1747 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6962 -0.6281 -2.0843 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4490 -0.3755 -0.9986 O 0 0 0 0 0 0 0 0 0 0 0 0 4.7754 0.6946 -0.2473 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6141 0.4989 0.8648 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9609 1.5889 1.6416 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5092 2.8590 1.3583 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6734 3.0832 0.2581 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3605 1.9675 -0.4791 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2326 4.2838 -0.0284 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5689 5.3072 0.7171 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1653 6.4824 0.4767 O 0 0 0 0 0 0 0 0 0 0 0 0 5.3892 5.1665 1.8188 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8803 3.9030 2.1579 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1267 -0.2345 -1.7639 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8748 -1.2663 -0.9577 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.3050 -1.2810 -1.3724 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2729 -0.5663 -0.8154 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6375 -0.6968 -1.3455 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6655 -1.1748 -0.3656 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3703 -2.5121 0.2152 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2788 -2.6970 1.5116 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4716 -1.5645 2.4378 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9821 -4.0348 2.0594 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9030 0.3243 0.3140 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2900 -2.5084 -1.3161 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8173 1.1541 0.1940 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7531 -0.1295 0.7455 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4266 -0.5788 0.4901 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8725 -0.7868 -3.2195 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0863 0.0826 -2.9238 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9967 -1.6313 -2.5797 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9494 -0.4963 1.0605 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6117 1.3900 2.4912 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7110 2.1186 -1.3420 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6831 5.9803 2.4461 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5192 3.7526 3.0061 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1622 -0.4372 -2.8441 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5250 0.7954 -1.6206 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7492 -1.1932 0.1173 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5613 -1.9458 -2.2129 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6401 -1.3719 -2.2054 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0035 0.2865 -1.7258 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6160 -1.3005 -0.9637 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9092 -0.4120 0.3861 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2275 -3.3534 -0.4493 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4230 -1.8816 3.5073 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6739 -0.8195 2.2609 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4719 -1.0963 2.2197 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2760 -3.8611 2.9255 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5246 -4.7105 1.3066 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8844 -4.4990 2.5466 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6006 -0.2748 1.1981 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1754 1.1115 0.0549 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8095 0.8950 0.6748 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4833 -2.6794 -0.7035 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 2 0 10 12 1 0 12 13 1 0 13 14 2 0 13 15 1 0 15 16 2 0 2 17 1 0 17 18 1 0 18 19 1 0 19 20 2 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 2 3 24 25 1 0 24 26 1 0 20 27 1 0 18 28 1 0 11 6 1 0 16 9 1 0 1 29 1 0 1 30 1 0 1 31 1 0 3 32 1 0 4 33 1 0 4 34 1 0 7 35 1 0 8 36 1 0 11 37 1 0 15 38 1 0 16 39 1 0 17 40 1 0 17 41 1 0 18 42 1 1 19 43 1 0 21 44 1 0 21 45 1 0 22 46 1 0 22 47 1 0 23 48 1 0 25 49 1 0 25 50 1 0 25 51 1 0 26 52 1 0 26 53 1 0 26 54 1 0 27 55 1 0 27 56 1 0 27 57 1 0 28 58 1 0 M END

Standard InCHIKey	IANTXARIIJNAIU-VYEGOAANSA-N
Standard InCHI	InChI=1S/C24H30O4/c1-17(2)6-5-7-18(3)14-21(25)15-19(4)12-13-27-22-10-8-20-9-11-24(26)28-23(20)16-22/h6,8-12,14,16,21,25H,5,7,13,15H2,1-4H3/b18-14+,19-12+/t21-/m1/s1
SMILES	C/C(=CCOc1ccc2c(c1)oc(=O)cc2)/C[C@@H](/C=C(/CCC=C(C)C)C)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	382.21	Volume:	420.616 ? Van der Waals volume.
Dense:	0.909	LogP:	4.419 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.831 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.537 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	9.0	Rigid Bonds:	15.0
TPSA:	59.67 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	1.0	Rings:	2.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.455	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.37	Fsp³:	0.375
MCE-18:	28.0 ? 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:	0.994	Fluc inhibitor:	0.513 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.884 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.469 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.332	Promiscuous compounds:	0.076

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.631	MDCK Permeability:	-4.671
Pgp-inhibitor:	0.55	Pgp-substrate:	0.0
PAMPA:	0.113 ? 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):	0.003
20% Bioavailability (F20%):	0.587	30% Bioavailability (F30%):	0.692
50% Bioavailability (F50%):	0.61

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.996
Plasma Protein Binding (PPB):	95.068%	Volume Distribution (VD):	0.072
Fu:	3.724% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.0
BSEP inhibitor:	0.999

ADMET: Metabolism

CYP1A2-inhibitor:	0.003	CYP1A2-substrate:	0.022
CYP2C19-inhibitor:	0.359	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.511	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.377	CYP2D6-substrate:	0.241
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.905
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.92
HLM stability:	0.997 ? 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):

7.891

Half-life (T1/2):

0.761

ADMET: Toxicity

hERG Blockers:	0.304	hERG Blockers (10um):	0.452
Human Hepatotoxicity (H-HT):	0.703	Drug-induced Liver Injury (DILI):	0.884
AMES Toxicity:	0.233	Rat Oral Acute Toxicity:	0.231
Maximum Recommended Daily Dose:	0.804	Skin Sensitization:	0.334
Carcinogencity:	0.709	Eye Corrosion:	0.0
Eye Irritation:	0.537	Respiratory Toxicity:	0.868
Drug-induced Neurotoxicity:	0.476	Ototoxicity:	0.557
Hematotoxicity:	0.318	Drug-induced Nephrotoxicity:	0.533
Genotoxicity:	0.802	RPMI-8226 Immunitoxicity:	0.115
A549 Cytotoxicity:	0.184	Hek293 Cytotoxicity:	0.38
BCF:	1.982 ? 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:	4.752 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.319 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.892 ? 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
NPO10996	Ferula assa-foetida	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19691312]
NPO10996	Ferula assa-foetida	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[31707845]
NPO10996	Ferula assa-foetida	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[385653815]
NPO10996	Ferula assa-foetida	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO10996	Ferula assa-foetida	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

Activity Type	# Activity
IC50	1
IC90	1

Activity Type	# Activity
Organism	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
NPT742	Organism	Influenza A virus	Influenza A virus	IC50	=	0.36	ug.mL-1	PMID[26135471]
NPT742	Organism	Influenza A virus	Influenza A virus	IC90	=	0.62	ug.mL-1	PMID[17950610]

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 NPC258567 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	12997
0.1-0.2	34664
0.2-0.3	1931
0.3-0.4	197
0.4-0.5	33
0.5-0.6	18
0.6-0.7	12
0.7-0.8	0
0.8-0.85	1
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8548	High Similarity	NPC224774
0.8065	Intermediate Similarity	NPC180006
0.7812	Intermediate Similarity	NPC235190
0.7286	Intermediate Similarity	NPC267336
0.7286	Intermediate Similarity	NPC272650
0.72	Intermediate Similarity	NPC469453
0.6957	Remote Similarity	NPC2363
0.6912	Remote Similarity	NPC479428
0.6912	Remote Similarity	NPC121740
0.6912	Remote Similarity	NPC113098
0.6912	Remote Similarity	NPC33279
0.6714	Remote Similarity	NPC29734
0.6613	Remote Similarity	NPC281356
0.6316	Remote Similarity	NPC131198
0.625	Remote Similarity	NPC469449
0.625	Remote Similarity	NPC479429
0.625	Remote Similarity	NPC479314
0.6143	Remote Similarity	NPC479427
0.5946	Remote Similarity	NPC479315
0.5833	Remote Similarity	NPC241341
0.5811	Remote Similarity	NPC601571
0.5696	Remote Similarity	NPC481285
0.5679	Remote Similarity	NPC471068
0.5679	Remote Similarity	NPC471069
0.5679	Remote Similarity	NPC471070
0.5541	Remote Similarity	NPC290764
0.5529	Remote Similarity	NPC471072
0.5526	Remote Similarity	NPC164148
0.5526	Remote Similarity	NPC43500
0.5479	Remote Similarity	NPC19242
0.5432	Remote Similarity	NPC14697
0.5341	Remote Similarity	NPC471071
0.5132	Remote Similarity	NPC233018
0.5125	Remote Similarity	NPC269495
0.506	Remote Similarity	NPC20631
0.506	Remote Similarity	NPC93640

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC258567 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3839
0.1-0.2	5186
0.2-0.3	122
0.3-0.4	3
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