NPASS Compound

Natural Product: NPC469453

Natural Product ID	NPC469453
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	8'-Acetoxy-5's-Hydroxyumbelliprenin
IUPAC Name	[(6E,8S,10E)-8-hydroxy-2,6,10-trimethyl-12-(2-oxochromen-7-yl)oxydodeca-2,6,10-trien-5-yl] acetate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1079138
PubChem CID	46882953
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 64 65 0 0 0 0 0 0 0 0999 V2000 -6.6444 -1.1436 2.5647 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0402 0.0590 1.8987 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5309 1.2086 2.0512 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9171 -0.0339 1.0861 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3773 1.1126 0.4779 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9073 1.2785 0.7795 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3825 0.3561 1.5934 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9519 0.4218 1.9558 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.1672 -0.1463 0.8198 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3020 -0.1426 1.0470 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1398 0.5158 0.2555 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6125 0.5375 0.4591 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2857 -0.0055 -0.6814 O 0 0 0 0 0 0 0 0 0 0 0 0 5.6591 -0.0694 -0.6798 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3898 0.3815 0.4024 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7701 0.3216 0.4136 C 0 0 0 0 0 0 0 0 0 0 0 0 8.4648 -0.1887 -0.6519 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7225 -0.6410 -1.7385 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3384 -0.5880 -1.7653 C 0 0 0 0 0 0 0 0 0 0 0 0 8.3771 -1.1263 -2.7524 O 0 0 0 0 0 0 0 0 0 0 0 0 9.6786 -1.2172 -2.8191 C 0 0 0 0 0 0 0 0 0 0 0 0 10.2515 -1.6992 -3.8343 O 0 0 0 0 0 0 0 0 0 0 0 0 10.4723 -0.7916 -1.7865 C 0 0 0 0 0 0 0 0 0 0 0 0 9.8467 -0.2660 -0.6794 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8362 -0.9154 2.1985 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7472 -0.3440 3.1025 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1288 2.3876 0.2036 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5546 0.9321 -1.0357 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0044 0.8038 -1.2779 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4892 -0.2853 -1.8353 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.9678 -0.3890 -2.0701 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5827 -1.3997 -2.2275 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1314 -2.0259 2.1287 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7347 -1.2070 2.3483 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4198 -1.1253 3.6390 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9381 2.0450 0.7217 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9849 -0.4453 1.9962 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6343 1.4498 2.2360 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4483 0.3880 -0.1072 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5414 -1.2005 0.6699 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6845 1.0527 -0.5700 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9388 0.0791 1.3939 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8967 1.6159 0.4725 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8448 0.7890 1.2540 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3173 0.6812 1.2730 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7961 -0.9478 -2.6248 H 0 0 0 0 0 0 0 0 0 0 0 0 11.5565 -0.8678 -1.8432 H 0 0 0 0 0 0 0 0 0 0 0 0 10.4048 0.0931 0.1801 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7246 -1.4843 1.7870 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1019 -0.2959 3.0579 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0688 -1.6634 2.5386 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4458 -1.0541 3.1193 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8126 2.2153 -0.8483 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8362 3.2672 0.1401 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2850 2.7291 0.7968 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1205 1.7974 -1.5815 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0698 -0.0237 -1.3116 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6553 1.6107 -0.9929 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3970 0.6201 -2.2115 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0831 -1.0157 -2.9948 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.4825 -0.9086 -1.2311 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2004 -2.2314 -2.6295 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8282 -1.0347 -2.9342 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0391 -1.8260 -1.3525 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 2 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 18 20 1 0 20 21 1 0 21 22 2 0 21 23 1 0 23 24 2 0 10 25 1 0 8 26 1 0 6 27 1 0 5 28 1 0 28 29 1 0 29 30 2 3 30 31 1 0 30 32 1 0 19 14 1 0 24 17 1 0 1 33 1 0 1 34 1 0 1 35 1 0 5 36 1 0 7 37 1 0 8 38 1 1 9 39 1 0 9 40 1 0 11 41 1 0 12 42 1 0 12 43 1 0 15 44 1 0 16 45 1 0 19 46 1 0 23 47 1 0 24 48 1 0 25 49 1 0 25 50 1 0 25 51 1 0 26 52 1 0 27 53 1 0 27 54 1 0 27 55 1 0 28 56 1 0 28 57 1 0 29 58 1 0 31 59 1 0 31 60 1 0 31 61 1 0 32 62 1 0 32 63 1 0 32 64 1 0 M END

Standard InCHIKey	GPZNNGDJDDVSLA-JWINZSDRSA-N
Standard InCHI	InChI=1S/C26H32O6/c1-17(2)6-10-24(31-20(5)27)19(4)15-22(28)14-18(3)12-13-30-23-9-7-21-8-11-26(29)32-25(21)16-23/h6-9,11-12,15-16,22,24,28H,10,13-14H2,1-5H3/b18-12+,19-15+/t22-,24?/m0/s1
SMILES	CC(=O)OC(/C(=C/[C@H](C/C(=C/COc1ccc2c(c1)oc(=O)cc2)/C)O)/C)CC=C(C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	440.22	Volume:	470.152 ? Van der Waals volume.
Dense:	0.936	LogP:	4.136 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.619 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.552 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	11.0	Rigid Bonds:	16.0
TPSA:	85.97 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	1.0	Rings:	2.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.314	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.87	Fsp³:	0.385
MCE-18:	32.0 ? 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:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.972	Fluc inhibitor:	0.18 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.841 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.411 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.276	Promiscuous compounds:	0.039

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.618	MDCK Permeability:	-4.539
Pgp-inhibitor:	0.013	Pgp-substrate:	0.001
PAMPA:	0.771 ? 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%):	0.746	30% Bioavailability (F30%):	0.721
50% Bioavailability (F50%):	0.773

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.999
Plasma Protein Binding (PPB):	93.619%	Volume Distribution (VD):	0.163
Fu:	5.569% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.0
BSEP inhibitor:	0.997

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.005
CYP2C19-inhibitor:	0.077	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.01	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.015	CYP2D6-substrate:	0.011
CYP3A4-inhibitor:	0.003	CYP3A4-substrate:	0.015
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.817
HLM stability:	0.999 ? 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):

6.625

Half-life (T1/2):

0.527

ADMET: Toxicity

hERG Blockers:	0.137	hERG Blockers (10um):	0.378
Human Hepatotoxicity (H-HT):	0.716	Drug-induced Liver Injury (DILI):	0.972
AMES Toxicity:	0.428	Rat Oral Acute Toxicity:	0.55
Maximum Recommended Daily Dose:	0.912	Skin Sensitization:	0.136
Carcinogencity:	0.732	Eye Corrosion:	0.0
Eye Irritation:	0.048	Respiratory Toxicity:	0.596
Drug-induced Neurotoxicity:	0.449	Ototoxicity:	0.666
Hematotoxicity:	0.356	Drug-induced Nephrotoxicity:	0.575
Genotoxicity:	0.991	RPMI-8226 Immunitoxicity:	0.111
A549 Cytotoxicity:	0.195	Hek293 Cytotoxicity:	0.463
BCF:	1.254 ? 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:	4.051 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.696 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.191 ? 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	7
IC90	1

Activity Type	# Activity
Cell line	5
Organism	2
Non-molecular	1

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
NPT65	Cell line	HepG2	Homo sapiens	IC50	=	15.59	ug.mL-1	PubChem BioAssay data set
NPT82	Cell line	MDA-MB-231	Homo sapiens	IC50	>	20.0	ug.mL-1	PMID[23743282]
NPT83	Cell line	MCF7	Homo sapiens	IC50	>	20.0	ug.mL-1	PMID[9358635]
NPT1031	Cell line	Ca9-22	Homo sapiens	IC50	=	14.23	ug.mL-1	DrugMatrix in vivo data: Pathology
NPT81	Cell line	A549	Homo sapiens	IC50	>	20.0	ug.mL-1	PMID[22705020]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	9.82	ug.mL-1	PMID[19691312]
NPT742	Organism	Influenza A virus	Influenza A virus	IC50	=	0.81	ug.mL-1	PMID[26135471]
NPT742	Organism	Influenza A virus	Influenza A virus	IC90	=	1.56	ug.mL-1	PMID[18440233]

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 NPC469453 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	9599
0.1-0.2	37836
0.2-0.3	2170
0.3-0.4	196
0.4-0.5	28
0.5-0.6	18
0.6-0.7	7
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
0.7681	Intermediate Similarity	NPC224774
0.72	Intermediate Similarity	NPC258567
0.6267	Remote Similarity	NPC33279
0.6104	Remote Similarity	NPC2363
0.6104	Remote Similarity	NPC29734
0.6081	Remote Similarity	NPC180006
0.6053	Remote Similarity	NPC479428
0.6053	Remote Similarity	NPC121740
0.6053	Remote Similarity	NPC113098
0.5976	Remote Similarity	NPC481285
0.5942	Remote Similarity	NPC281356
0.5921	Remote Similarity	NPC235190
0.5802	Remote Similarity	NPC267336
0.5802	Remote Similarity	NPC272650
0.5789	Remote Similarity	NPC479427
0.5765	Remote Similarity	NPC471068
0.5765	Remote Similarity	NPC471069
0.5765	Remote Similarity	NPC471070
0.5696	Remote Similarity	NPC479429
0.5696	Remote Similarity	NPC479314
0.55	Remote Similarity	NPC601571
0.5444	Remote Similarity	NPC471072
0.5432	Remote Similarity	NPC479315
0.5412	Remote Similarity	NPC131198
0.5269	Remote Similarity	NPC471071
0.5222	Remote Similarity	NPC469449
0.5172	Remote Similarity	NPC14697

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC469453 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3580
0.1-0.2	5445
0.2-0.3	124
0.3-0.4	1
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