NPASS Compound

Natural Product: NPC288910

Natural Product ID	NPC288910
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	5,7-Dihydroxy-4-[(1S)-1-Hydroxypentyl]-8-(3-Methylbutanoyl)-6-(3-Methylbut-2-Enyl)Chromen-2-One
IUPAC Name	5,7-dihydroxy-4-[(1S)-1-hydroxypentyl]-8-(3-methylbutanoyl)-6-(3-methylbut-2-enyl)chromen-2-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1689176
PubChem CID	51040688
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000145] Coumarins and derivatives [CHEMONTID:0002908] Hydroxycoumarins [CHEMONTID:0002909] 7-hydroxycoumarins

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 62 63 0 0 0 0 0 0 0 0999 V2000 4.2928 -1.5934 2.0087 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8431 -2.2016 0.7233 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8509 -2.0282 -0.3764 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5559 -0.5312 -0.6345 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5482 -0.3845 -1.7402 C 0 0 1 0 0 0 0 0 0 0 0 0 1.2461 -1.0013 -1.4846 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9729 -2.3122 -1.8410 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2259 -2.9097 -1.6077 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4361 -4.1339 -1.9571 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1568 -2.2217 -1.0248 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9697 -0.9791 -0.6602 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2325 -0.2853 -0.8614 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3793 1.0150 -0.4604 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5843 1.6619 -0.6774 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6670 1.6805 0.1585 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4579 3.1096 0.5704 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5479 4.0323 -0.5498 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4278 4.8470 -0.8906 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7430 4.9544 -0.2058 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2553 5.7823 -2.0741 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8491 1.0090 0.3599 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0167 -0.2955 -0.0347 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2688 -1.0249 0.1721 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1379 -0.9663 -0.7474 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4961 -1.7901 1.4009 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8719 -2.4490 1.3340 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8734 -3.3568 0.1342 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9786 -3.3203 2.5802 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9006 1.6646 0.9774 O 0 0 0 0 0 0 0 0 0 0 0 0 2.6332 0.7012 -2.5571 O 0 0 0 0 0 0 0 0 0 0 0 0 4.8877 -2.0481 2.8403 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2348 -1.9013 2.0854 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4427 -0.5026 1.9585 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7799 -1.6540 0.4858 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0739 -3.2605 0.8432 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3296 -2.3955 -1.3217 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9376 -2.5896 -0.2040 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1320 -0.2026 0.3324 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5383 -0.0968 -0.8831 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0074 -1.1521 -2.5021 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7477 -2.8818 -2.3228 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1301 1.9980 0.1084 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3081 3.3191 1.2834 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4730 3.1668 1.1679 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4609 4.0510 -1.1307 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1405 6.0044 -0.3068 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7125 4.7032 0.8693 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4441 4.2481 -0.7337 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7394 5.3235 -2.9541 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8274 5.9563 -2.2546 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7218 6.7543 -1.8413 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4205 -1.1183 2.2983 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7778 -2.6115 1.5726 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6691 -1.6835 1.2995 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8703 -3.5284 -0.2996 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2828 -4.3662 0.3680 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5775 -2.9016 -0.6167 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0086 -3.2299 2.9697 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2825 -2.9575 3.3823 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6785 -4.3676 2.3694 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5590 2.2024 0.3961 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5393 1.0496 -2.5210 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 7 8 1 0 8 9 2 0 8 10 1 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 1 0 13 15 2 0 15 16 1 0 16 17 1 0 17 18 2 3 18 19 1 0 18 20 1 0 15 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 23 25 1 0 25 26 1 0 26 27 1 0 26 28 1 0 21 29 1 0 5 30 1 0 12 6 1 0 22 11 1 0 1 31 1 0 1 32 1 0 1 33 1 0 2 34 1 0 2 35 1 0 3 36 1 0 3 37 1 0 4 38 1 0 4 39 1 0 5 40 1 6 7 41 1 0 14 42 1 0 16 43 1 0 16 44 1 0 17 45 1 0 19 46 1 0 19 47 1 0 19 48 1 0 20 49 1 0 20 50 1 0 20 51 1 0 25 52 1 0 25 53 1 0 26 54 1 0 27 55 1 0 27 56 1 0 27 57 1 0 28 58 1 0 28 59 1 0 28 60 1 0 29 61 1 0 30 62 1 0 M END

Standard InCHIKey	KDXSRMVJFBSRCC-KRWDZBQOSA-N
Standard InCHI	InChI=1S/C24H32O6/c1-6-7-8-17(25)16-12-19(27)30-24-20(16)22(28)15(10-9-13(2)3)23(29)21(24)18(26)11-14(4)5/h9,12,14,17,25,28-29H,6-8,10-11H2,1-5H3/t17-/m0/s1
SMILES	CCCC[C@@H](c1cc(=O)oc2c1c(O)c(CC=C(C)C)c(c2C(=O)CC(C)C)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	416.22	Volume:	440.833 ? Van der Waals volume.
Dense:	0.944	LogP:	4.596 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.739 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.257 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	9.0	Rigid Bonds:	14.0
TPSA:	107.97 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	3.0	Rings:	2.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.296	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.569	Fsp³:	0.5
MCE-18:	36.0 ? 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:	0.79	Fluc inhibitor:	0.064 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.936 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.616 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.073	Promiscuous compounds:	0.145

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.95	MDCK Permeability:	-4.675
Pgp-inhibitor:	0.541	Pgp-substrate:	0.038
PAMPA:	0.456 ? 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):	0.012
20% Bioavailability (F20%):	0.433	30% Bioavailability (F30%):	0.583
50% Bioavailability (F50%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.009	MRP1:	0.99
Plasma Protein Binding (PPB):	94.478%	Volume Distribution (VD):	0.037
Fu:	5.176% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.973
OATP1B3 inhibitor:	0.957	BCRP inhibitor:	0.073
BSEP inhibitor:	0.998

ADMET: Metabolism

CYP1A2-inhibitor:	0.008	CYP1A2-substrate:	0.995
CYP2C19-inhibitor:	0.706	CYP2C19-substrate:	0.988
CYP2C9-inhibitor:	0.021	CYP2C9-substrate:	0.432
CYP2D6-inhibitor:	0.006	CYP2D6-substrate:	0.165
CYP3A4-inhibitor:	0.117	CYP3A4-substrate:	0.97
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
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):

4.309

Half-life (T1/2):

1.027

ADMET: Toxicity

hERG Blockers:	0.076	hERG Blockers (10um):	0.321
Human Hepatotoxicity (H-HT):	0.793	Drug-induced Liver Injury (DILI):	0.414
AMES Toxicity:	0.315	Rat Oral Acute Toxicity:	0.667
Maximum Recommended Daily Dose:	0.574	Skin Sensitization:	0.96
Carcinogencity:	0.27	Eye Corrosion:	0.006
Eye Irritation:	0.728	Respiratory Toxicity:	0.937
Drug-induced Neurotoxicity:	0.179	Ototoxicity:	0.516
Hematotoxicity:	0.413	Drug-induced Nephrotoxicity:	0.824
Genotoxicity:	0.666	RPMI-8226 Immunitoxicity:	0.181
A549 Cytotoxicity:	0.702	Hek293 Cytotoxicity:	0.362
BCF:	1.849 ? 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:	4.701 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.33 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.853 ? 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
NPO21645	Mammea americana	Species	Calophyllaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21214226]
NPO21645	Mammea americana	Species	Calophyllaceae	Eukaryota	n.a.	stem	n.a.	PMID[21214226]
NPO21645	Mammea americana	Species	Calophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21645	Mammea americana	Species	Calophyllaceae	Eukaryota	Fruit	n.a.	n.a.	Database[FooDB]
NPO21645	Mammea americana	Species	Calophyllaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO21645	Mammea americana	Species	Calophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO21645	Mammea americana	Species	Calophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO21645	Mammea americana	Species	Calophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO21645	Mammea americana	Species	Calophyllaceae	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	4

Activity Type	# Activity
Cell line	2
Protein family	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
NPT396	Cell line	T47D	Homo sapiens	IC50	=	910.0	nM	PMID[21214226]
NPT306	Cell line	PC-3	Homo sapiens	IC50	=	1140.0	nM	PMID[21214226]
NPT21802	Protein family	Hypoxia inducible factors; HIF-1-alpha, HIF-2-alpha	Homo sapiens	IC50	=	1720.0	nM	PMID[21214226]
NPT21802	Protein family	Hypoxia inducible factors; HIF-1-alpha, HIF-2-alpha	Homo sapiens	IC50	=	1810.0	nM	PMID[21214226]

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 NPC288910 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	9038
0.1-0.2	38463
0.2-0.3	2229
0.3-0.4	92
0.4-0.5	13
0.5-0.6	13
0.6-0.7	5
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8333	Intermediate Similarity	NPC133060
0.7857	Intermediate Similarity	NPC118059
0.7463	Intermediate Similarity	NPC470909
0.7246	Intermediate Similarity	NPC19476
0.7059	Intermediate Similarity	NPC183639
0.6986	Remote Similarity	NPC33653
0.6714	Remote Similarity	NPC96216
0.6533	Remote Similarity	NPC470554
0.6351	Remote Similarity	NPC483432
0.6111	Remote Similarity	NPC294432
0.5946	Remote Similarity	NPC219584
0.589	Remote Similarity	NPC474939
0.5854	Remote Similarity	NPC307895
0.5753	Remote Similarity	NPC131782
0.5753	Remote Similarity	NPC474624
0.5584	Remote Similarity	NPC196137
0.5455	Remote Similarity	NPC241975
0.5375	Remote Similarity	NPC184738
0.5316	Remote Similarity	NPC470556
0.5185	Remote Similarity	NPC483434
0.5176	Remote Similarity	NPC112829
0.5132	Remote Similarity	NPC199458
0.5059	Remote Similarity	NPC181388

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC288910 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	2559
0.1-0.2	6510
0.2-0.3	81
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