NPASS Compound

Natural Product: NPC469449

Natural Product ID	NPC469449
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	10'r-Acetoxy-11'-Hydroxyumbelliprenin
IUPAC Name	[(3R,6E,10E)-2-hydroxy-2,6,10-trimethyl-12-(2-oxochromen-7-yl)oxydodeca-6,10-dien-3-yl] hydrogen carbonate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1079039
PubChem CID	46882952
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 -6.2756 3.6092 -2.1781 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.2664 2.8574 -1.0102 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6871 3.4360 0.0374 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.8306 1.5512 -0.9569 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.8361 0.8281 0.2340 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.8032 -0.3257 0.2199 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7381 -1.0379 1.4066 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.2233 0.2963 0.2256 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7447 -1.1867 -0.9965 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4945 0.4248 0.7554 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7804 -0.4319 -0.2256 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4186 -0.8371 0.2591 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3450 -0.4948 -0.4429 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0539 -0.8566 -0.0341 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8887 0.3795 0.1760 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2486 -0.0111 0.6081 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7053 0.3719 1.7730 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9565 0.1617 2.4440 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0184 -0.5143 1.9360 O 0 0 0 0 0 0 0 0 0 0 0 0 5.8646 -0.1685 0.9005 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7727 1.0050 0.1960 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6467 1.3166 -0.8428 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6464 0.4430 -1.2013 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7493 -0.7406 -0.5004 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8743 -1.0443 0.5340 C 0 0 0 0 0 0 0 0 0 0 0 0 8.7100 -1.5636 -0.8561 O 0 0 0 0 0 0 0 0 0 0 0 0 9.5565 -1.3242 -1.8202 C 0 0 0 0 0 0 0 0 0 0 0 0 10.4387 -2.2179 -2.0536 O 0 0 0 0 0 0 0 0 0 0 0 0 9.4959 -0.1608 -2.5475 C 0 0 0 0 0 0 0 0 0 0 0 0 8.5162 0.7547 -2.2362 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0676 -0.8880 -0.2467 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2157 -1.6121 1.5019 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7888 4.4647 -2.2952 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2493 1.5395 1.0317 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7682 -0.3538 2.1409 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1978 1.2166 0.8563 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.9486 -0.4511 0.5684 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.4401 0.5326 -0.8370 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0783 -0.7423 -1.7510 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4963 -2.2516 -0.7516 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7434 -1.2748 -1.5167 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9137 1.3257 1.0461 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6923 -0.2013 1.6713 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3382 -1.4046 -0.2920 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7074 -0.0221 -1.2342 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4834 0.0705 -1.3508 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0764 -1.4657 0.8682 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5041 -1.4447 -0.8575 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9982 0.9561 -0.7888 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4344 1.0266 0.9537 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9693 0.9916 2.3766 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2863 1.1758 2.9030 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6889 -0.3842 3.4310 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9962 1.6973 0.4652 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5698 2.2436 -1.3952 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9849 -1.9878 1.0655 H 0 0 0 0 0 0 0 0 0 0 0 0 10.1949 0.0383 -3.3445 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4170 1.7055 -2.7834 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4038 -1.5639 -0.8850 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6077 -1.6688 0.3714 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6818 -0.3813 -0.9830 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5100 -1.0452 2.1510 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1464 -1.7248 2.0931 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8624 -2.6353 1.2748 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 1 0 6 8 1 0 6 9 1 0 5 10 1 0 10 11 1 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 24 26 1 0 26 27 1 0 27 28 2 0 27 29 1 0 29 30 2 0 16 31 1 0 12 32 1 0 25 20 1 0 30 23 1 0 1 33 1 0 5 34 1 1 7 35 1 0 8 36 1 0 8 37 1 0 8 38 1 0 9 39 1 0 9 40 1 0 9 41 1 0 10 42 1 0 10 43 1 0 11 44 1 0 11 45 1 0 13 46 1 0 14 47 1 0 14 48 1 0 15 49 1 0 15 50 1 0 17 51 1 0 18 52 1 0 18 53 1 0 21 54 1 0 22 55 1 0 25 56 1 0 29 57 1 0 30 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	UVQBYRWBSPMKKU-PKAURPTQSA-N
Standard InCHI	InChI=1S/C25H32O7/c1-17(8-12-22(25(3,4)29)32-24(27)28)6-5-7-18(2)14-15-30-20-11-9-19-10-13-23(26)31-21(19)16-20/h6,9-11,13-14,16,22,29H,5,7-8,12,15H2,1-4H3,(H,27,28)/b17-6+,18-14+/t22-/m1/s1
SMILES	OC(=O)O[C@@H](C(O)(C)C)CC/C(=C/CC/C(=C/COc1ccc2c(c1)oc(=O)cc2)/C)/C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	444.21	Volume:	464.283 ? Van der Waals volume.
Dense:	0.957	LogP:	5.277 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.741 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.019 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	12.0	Rigid Bonds:	15.0
TPSA:	106.2 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	2.0	Rings:	2.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.269	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.516	Fsp³:	0.44
MCE-18:	34.0 ? 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:	0.516	Fluc inhibitor:	0.5 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.968 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.392 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.175	Promiscuous compounds:	0.042

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.808	MDCK Permeability:	-4.66
Pgp-inhibitor:	0.974	Pgp-substrate:	0.0
PAMPA:	0.052 ? 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):	0.005
20% Bioavailability (F20%):	0.693	30% Bioavailability (F30%):	0.545
50% Bioavailability (F50%):	0.223

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.998
Plasma Protein Binding (PPB):	92.557%	Volume Distribution (VD):	-0.343
Fu:	4.83% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.0
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.036	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.69	CYP2C19-substrate:	0.032
CYP2C9-inhibitor:	0.973	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.72	CYP2D6-substrate:	0.02
CYP3A4-inhibitor:	0.018	CYP3A4-substrate:	0.161
CYP2B6-substrate:	0.001	CYP2C8-inhibitor:	0.99
HLM stability:	0.117 ? 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):

0.78

Half-life (T1/2):

1.257

ADMET: Toxicity

hERG Blockers:	0.131	hERG Blockers (10um):	0.093
Human Hepatotoxicity (H-HT):	0.726	Drug-induced Liver Injury (DILI):	0.836
AMES Toxicity:	0.188	Rat Oral Acute Toxicity:	0.145
Maximum Recommended Daily Dose:	0.354	Skin Sensitization:	0.703
Carcinogencity:	0.364	Eye Corrosion:	0.0
Eye Irritation:	0.194	Respiratory Toxicity:	0.578
Drug-induced Neurotoxicity:	0.099	Ototoxicity:	0.549
Hematotoxicity:	0.375	Drug-induced Nephrotoxicity:	0.871
Genotoxicity:	0.985	RPMI-8226 Immunitoxicity:	0.053
A549 Cytotoxicity:	0.011	Hek293 Cytotoxicity:	0.137
BCF:	1.014 ? 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:	4.243 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.699 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.758 ? 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	>	20.0	ug.mL-1	PMID[16759112]
NPT82	Cell line	MDA-MB-231	Homo sapiens	IC50	>	20.0	ug.mL-1	PMID[23822611]
NPT83	Cell line	MCF7	Homo sapiens	IC50	>	20.0	ug.mL-1	DrugMatrix in vivo data: Biochemistry
NPT1031	Cell line	Ca9-22	Homo sapiens	IC50	>	20.0	ug.mL-1	PMID[20413315]
NPT81	Cell line	A549	Homo sapiens	IC50	>	20.0	ug.mL-1	PMID[19877653]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	19.79	ug.mL-1	PMID[19691312]
NPT742	Organism	Influenza A virus	Influenza A virus	IC50	=	0.94	ug.mL-1	PMID[21053938]
NPT742	Organism	Influenza A virus	Influenza A virus	IC90	=	1.98	ug.mL-1	PMID[22037378]

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 NPC469449 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	9748
0.1-0.2	38453
0.2-0.3	1469
0.3-0.4	129
0.4-0.5	28
0.5-0.6	14
0.6-0.7	13
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
0.72	Intermediate Similarity	NPC267336
0.72	Intermediate Similarity	NPC272650
0.7183	Intermediate Similarity	NPC235190
0.6901	Remote Similarity	NPC180006
0.6447	Remote Similarity	NPC479429
0.6447	Remote Similarity	NPC479314
0.64	Remote Similarity	NPC113098
0.6265	Remote Similarity	NPC471068
0.6265	Remote Similarity	NPC471069
0.6265	Remote Similarity	NPC471070
0.625	Remote Similarity	NPC258567
0.6234	Remote Similarity	NPC2363
0.6234	Remote Similarity	NPC29734
0.6184	Remote Similarity	NPC479428
0.6184	Remote Similarity	NPC121740
0.6092	Remote Similarity	NPC471072
0.5974	Remote Similarity	NPC33279
0.5889	Remote Similarity	NPC471071
0.5769	Remote Similarity	NPC224774
0.5714	Remote Similarity	NPC131198
0.5714	Remote Similarity	NPC481285
0.5634	Remote Similarity	NPC281356
0.5556	Remote Similarity	NPC164148
0.5556	Remote Similarity	NPC43500
0.5513	Remote Similarity	NPC479427
0.5465	Remote Similarity	NPC14697
0.5443	Remote Similarity	NPC241341
0.5432	Remote Similarity	NPC601571
0.5366	Remote Similarity	NPC479315
0.5222	Remote Similarity	NPC469453

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC469449 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	2671
0.1-0.2	6331
0.2-0.3	147
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