NPASS Compound

Natural Product: NPC109371

Natural Product ID	NPC109371
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(3R,5R)-3-Acetoxy-5-Hydroxy-1,7-Bis(3,4-Dihydroxyphenyl)Heptane
IUPAC Name	[(3R,5R)-1,7-bis(3,4-dihydroxyphenyl)-5-hydroxyheptan-3-yl] acetate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1824574
PubChem CID	54577120
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0002650] Diarylheptanoids [CHEMONTID:0002651] Linear diarylheptanoids

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 54 55 0 0 0 0 0 0 0 0999 V2000 -0.6519 1.5495 1.6665 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0381 1.3748 0.3686 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.3040 0.3517 -0.3701 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2002 0.6828 -0.4903 C 0 0 2 0 0 0 0 0 0 0 0 0 1.7752 -0.3973 -1.2222 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1495 -0.2571 -2.5511 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0077 0.8159 -3.1797 O 0 0 0 0 0 0 0 0 0 0 0 0 2.7370 -1.4197 -3.2492 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8586 0.9775 0.7814 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3131 1.2821 0.8317 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2572 0.2569 0.4110 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8098 0.2403 -0.8302 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7030 -0.7370 -1.2093 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0773 -1.7485 -0.3379 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5300 -1.7532 0.9270 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6459 -0.7722 1.2794 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8808 -2.7582 1.8414 O 0 0 0 0 0 0 0 0 0 0 0 0 6.9716 -2.7460 -0.6850 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5499 1.2527 0.2416 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0800 0.0783 1.0257 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5656 0.0595 0.8281 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1576 -0.6342 -0.2068 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5163 -0.6699 -0.4117 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.3561 0.0255 0.4619 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7713 0.7124 1.4864 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4088 0.7445 1.6868 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.6038 1.4075 2.3603 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.7138 0.0127 0.2890 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9023 2.4353 2.0359 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8200 2.3687 -0.1484 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6653 0.2249 -1.4257 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3110 -0.6671 0.0747 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2778 1.5666 -1.1902 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8285 -1.4242 -3.2999 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3871 -2.3585 -2.7293 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3270 -1.5152 -4.2964 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6379 0.1681 1.5510 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3728 1.9387 1.2230 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5189 2.1810 0.1547 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5829 1.7067 1.8449 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5839 0.9926 -1.5978 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1335 -0.7345 -2.2025 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2065 -0.7606 2.2685 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3206 -3.6122 1.5337 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8090 -2.5833 -1.2062 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9767 2.1714 0.6905 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8355 1.2270 -0.8141 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6947 -0.8861 0.6869 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9196 0.2054 2.1126 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5302 -1.1831 -0.9000 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9981 -1.2030 -1.2098 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9376 1.2928 2.5049 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.2947 2.0301 1.9771 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.3003 -0.7332 0.6183 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 4 9 1 0 9 10 1 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 15 17 1 0 14 18 1 0 2 19 1 0 19 20 1 0 20 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 25 27 1 0 24 28 1 0 16 11 1 0 26 21 1 0 1 29 1 0 2 30 1 6 3 31 1 0 3 32 1 0 4 33 1 6 8 34 1 0 8 35 1 0 8 36 1 0 9 37 1 0 9 38 1 0 10 39 1 0 10 40 1 0 12 41 1 0 13 42 1 0 16 43 1 0 17 44 1 0 18 45 1 0 19 46 1 0 19 47 1 0 20 48 1 0 20 49 1 0 22 50 1 0 23 51 1 0 26 52 1 0 27 53 1 0 28 54 1 0 M END

Standard InCHIKey	LPQAWINMKZEZOZ-IAGOWNOFSA-N
Standard InCHI	InChI=1S/C21H26O7/c1-13(22)28-17(7-3-15-5-9-19(25)21(27)11-15)12-16(23)6-2-14-4-8-18(24)20(26)10-14/h4-5,8-11,16-17,23-27H,2-3,6-7,12H2,1H3/t16-,17-/m1/s1
SMILES	O[C@@H](C[C@H](OC(=O)C)CCc1ccc(c(c1)O)O)CCc1ccc(c(c1)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	390.17	Volume:	397.736 ? Van der Waals volume.
Dense:	0.981	LogP:	1.759 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.884 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.755 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	10.0	Rigid Bonds:	13.0
TPSA:	127.45 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	5.0	Rings:	2.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.329	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.26	Fsp³:	0.381
MCE-18:	30.0 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.688	Fluc inhibitor:	0.288 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.027 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.15 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.568	Promiscuous compounds:	0.576

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.184	MDCK Permeability:	-4.79
Pgp-inhibitor:	0.143	Pgp-substrate:	0.049
PAMPA:	0.117 ? 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):	0.05
20% Bioavailability (F20%):	0.999	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.45
Plasma Protein Binding (PPB):	74.305%	Volume Distribution (VD):	-0.325
Fu:	20.942% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.99
OATP1B3 inhibitor:	0.949	BCRP inhibitor:	0.834
BSEP inhibitor:	0.5

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.003	CYP2C19-substrate:	0.005
CYP2C9-inhibitor:	0.002	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.079	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	0.015	CYP3A4-substrate:	0.986
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
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):

18.054

Half-life (T1/2):

1.828

ADMET: Toxicity

hERG Blockers:	0.474	hERG Blockers (10um):	0.919
Human Hepatotoxicity (H-HT):	0.624	Drug-induced Liver Injury (DILI):	0.572
AMES Toxicity:	0.72	Rat Oral Acute Toxicity:	0.288
Maximum Recommended Daily Dose:	0.963	Skin Sensitization:	1.0
Carcinogencity:	0.275	Eye Corrosion:	0.002
Eye Irritation:	0.349	Respiratory Toxicity:	0.66
Drug-induced Neurotoxicity:	0.053	Ototoxicity:	0.974
Hematotoxicity:	0.271	Drug-induced Nephrotoxicity:	0.665
Genotoxicity:	0.848	RPMI-8226 Immunitoxicity:	0.02
A549 Cytotoxicity:	1.0	Hek293 Cytotoxicity:	0.876
BCF:	0.94 ? 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:	3.708 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.033 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.643 ? 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
NPO22741	Curcuma kwangsiensis	Species	Zingiberaceae	Eukaryota	n.a.	rhizome	n.a.	DOI[10.1021/np100392m]
NPO22901	Curcuma comosa	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1021/np100392m]
NPO22901	Curcuma comosa	Species	Zingiberaceae	Eukaryota	rhizomes	Kampaengsaen district, Nakhon Pathom province, Thailand	n.a.	PMID[18554915]
NPO22901	Curcuma comosa	Species	Zingiberaceae	Eukaryota	aerial parts	n.a.	n.a.	PMID[20196571]
NPO22741	Curcuma kwangsiensis	Species	Zingiberaceae	Eukaryota	Rhizomes	n.a.	n.a.	PMID[20879743]
NPO22741	Curcuma kwangsiensis	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21807513]
NPO22901	Curcuma comosa	Species	Zingiberaceae	Eukaryota	rhizomes	n.a.	n.a.	PMID[23910596]
NPO22901	Curcuma comosa	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[8176399]
NPO22741	Curcuma kwangsiensis	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO22901	Curcuma comosa	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO22741	Curcuma kwangsiensis	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO22741	Curcuma kwangsiensis	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO22741	Curcuma kwangsiensis	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO22741	Curcuma kwangsiensis	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO22741	Curcuma kwangsiensis	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22901	Curcuma comosa	Species	Zingiberaceae	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
Inhibition	6
IC50	1

Activity Type	# Activity
Individual protein	1
Cell line	1
Non-molecular	5

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT43	Individual protein	Tyrosinase	Agaricus bisporus	Inhibition	<	17.0	%	PMID[18077425]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT113	Cell line	RAW264.7	Mus musculus	IC50	=	35500.0	nM	PMID[16441076]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Inhibition	=	5.5	%	PMID[23910596]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Inhibition	=	4.5	%	PMID[23910596]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Inhibition	=	-5.7	%	PMID[23910596]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Inhibition	=	-9.9	%	PMID[23910596]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Inhibition	=	-1.6	%	PMID[23910596]

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 NPC109371 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	6523
0.1-0.2	37194
0.2-0.3	5767
0.3-0.4	298
0.4-0.5	51
0.5-0.6	15
0.6-0.7	5
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	2
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.9149	High Similarity	NPC470215
0.9149	High Similarity	NPC470214
0.7872	Intermediate Similarity	NPC63345
0.7174	Intermediate Similarity	NPC70084
0.66	Remote Similarity	NPC86198
0.6102	Remote Similarity	NPC231607
0.6	Remote Similarity	NPC200988
0.6	Remote Similarity	NPC145023
0.6	Remote Similarity	NPC34634
0.5714	Remote Similarity	NPC79715
0.5714	Remote Similarity	NPC108659
0.5686	Remote Similarity	NPC75039
0.5686	Remote Similarity	NPC98305
0.5652	Remote Similarity	NPC187583
0.5636	Remote Similarity	NPC25689
0.5593	Remote Similarity	NPC610
0.5593	Remote Similarity	NPC175799
0.5556	Remote Similarity	NPC265454
0.52	Remote Similarity	NPC179002
0.52	Remote Similarity	NPC257430
0.5161	Remote Similarity	NPC103398
0.5161	Remote Similarity	NPC608691
0.5098	Remote Similarity	NPC120982
0.507	Remote Similarity	NPC177035

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC109371 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	2704
0.1-0.2	6184
0.2-0.3	245
0.3-0.4	14
0.4-0.5	3
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