NPASS Compound

Natural Product: NPC470215

Natural Product ID	NPC470215
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-(3,4-Dihydroxyphenyl)-7-(4-Hydroxyphenyl)Heptane
IUPAC Name	[(3R,5R)-1-(3,4-dihydroxyphenyl)-5-hydroxy-7-(4-hydroxyphenyl)heptan-3-yl] acetate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1824577
PubChem CID	54577123
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 53 54 0 0 0 0 0 0 0 0999 V2000 1.2859 -1.7865 2.5522 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7676 -1.2219 1.3712 C 0 0 1 0 0 0 0 0 0 0 0 0 0.3310 0.1626 1.7230 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2572 0.9396 0.5630 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.6093 2.2220 1.1043 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0006 3.3841 0.6546 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8647 3.2670 -0.2392 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3769 4.7186 1.2279 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4547 0.2469 -0.0168 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5610 0.0679 0.9981 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7117 -0.6220 0.3592 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8105 -2.0180 0.3639 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8912 -2.5832 -0.2398 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8494 -1.8077 -0.8321 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7661 -0.4400 -0.8444 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6855 0.1477 -0.2417 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7566 0.3336 -1.4554 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.9436 -2.3977 -1.4425 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8368 -1.1882 0.3123 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0342 -0.3659 0.7330 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0456 -0.4014 -0.3834 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9758 -1.3989 -0.3671 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9416 -1.5006 -1.3598 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9039 -0.5364 -2.3593 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9722 0.4718 -2.3854 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0276 0.5421 -1.3829 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8447 -0.5857 -3.3801 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8517 -1.3830 3.3513 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0530 -1.8504 0.9620 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4180 0.1539 2.5778 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2004 0.6937 2.1702 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5201 1.0869 -0.2036 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4788 5.4822 0.4275 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4379 5.0570 1.9037 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2886 4.6236 1.8244 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1465 -0.7600 -0.3583 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8898 0.7908 -0.8714 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2476 -0.5756 1.8507 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9346 1.0392 1.3820 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0111 -2.5715 0.8537 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9757 -3.6613 -0.2411 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5918 1.2395 -0.2358 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5683 0.5586 -0.8649 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1569 -2.2022 -2.3933 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3992 -0.6955 -0.5862 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1597 -2.2272 0.0345 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7608 0.6957 0.9001 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5261 -0.7404 1.6350 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0139 -2.1585 0.4107 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6729 -2.2792 -1.3530 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9665 1.2188 -3.1865 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2678 1.3330 -1.3704 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8263 -0.5177 -3.2154 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 24 27 1 0 16 11 1 0 26 21 1 0 1 28 1 0 2 29 1 6 3 30 1 0 3 31 1 0 4 32 1 6 8 33 1 0 8 34 1 0 8 35 1 0 9 36 1 0 9 37 1 0 10 38 1 0 10 39 1 0 12 40 1 0 13 41 1 0 16 42 1 0 17 43 1 0 18 44 1 0 19 45 1 0 19 46 1 0 20 47 1 0 20 48 1 0 22 49 1 0 23 50 1 0 25 51 1 0 26 52 1 0 27 53 1 0 M END

Standard InCHIKey	WFGFERPBWVNUAJ-RTBURBONSA-N
Standard InCHI	InChI=1S/C21H26O6/c1-14(22)27-19(10-5-16-6-11-20(25)21(26)12-16)13-18(24)9-4-15-2-7-17(23)8-3-15/h2-3,6-8,11-12,18-19,23-26H,4-5,9-10,13H2,1H3/t18-,19-/m1/s1
SMILES	O[C@@H](C[C@H](OC(=O)C)CCc1ccc(c(c1)O)O)CCc1ccc(cc1)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	374.17	Volume:	388.945 ? Van der Waals volume.
Dense:	0.962	LogP:	1.912 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.99 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.045 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	10.0	Rigid Bonds:	13.0
TPSA:	107.22 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	4.0	Rings:	2.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.397	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.121	Fsp³:	0.381
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:	Rejected	GSK Rule:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.557	Fluc inhibitor:	0.155 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.026 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.106 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.565	Promiscuous compounds:	0.375

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.235	MDCK Permeability:	-4.795
Pgp-inhibitor:	0.425	Pgp-substrate:	0.313
PAMPA:	0.175 ? 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%):	0.965	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.332
Plasma Protein Binding (PPB):	78.519%	Volume Distribution (VD):	-0.281
Fu:	20.832% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.992
OATP1B3 inhibitor:	0.944	BCRP inhibitor:	0.531
BSEP inhibitor:	0.968

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.002
CYP2C19-inhibitor:	0.072	CYP2C19-substrate:	0.038
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.008
CYP2D6-inhibitor:	0.501	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	0.156	CYP3A4-substrate:	0.914
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.994 ? 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):

14.114

Half-life (T1/2):

1.436

ADMET: Toxicity

hERG Blockers:	0.599	hERG Blockers (10um):	0.893
Human Hepatotoxicity (H-HT):	0.68	Drug-induced Liver Injury (DILI):	0.326
AMES Toxicity:	0.655	Rat Oral Acute Toxicity:	0.258
Maximum Recommended Daily Dose:	0.95	Skin Sensitization:	0.999
Carcinogencity:	0.301	Eye Corrosion:	0.002
Eye Irritation:	0.295	Respiratory Toxicity:	0.656
Drug-induced Neurotoxicity:	0.282	Ototoxicity:	0.929
Hematotoxicity:	0.353	Drug-induced Nephrotoxicity:	0.863
Genotoxicity:	0.673	RPMI-8226 Immunitoxicity:	0.042
A549 Cytotoxicity:	0.997	Hek293 Cytotoxicity:	0.948
BCF:	0.946 ? 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:	3.722 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.867 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.547 ? 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	2

Activity Type	# Activity
Individual protein	1
Cell line	1
Non-molecular	6

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[11858756]

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	=	9520.0	nM	PMID[9784156]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	4910.0	nM	PMID[23910596]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Inhibition	=	59.9	%	PMID[23910596]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Inhibition	=	21.8	%	PMID[23910596]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Inhibition	=	27.3	%	PMID[23910596]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Inhibition	=	15.1	%	PMID[23910596]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Inhibition	=	15.4	%	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 NPC470215 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	7681
0.1-0.2	36134
0.2-0.3	5593
0.3-0.4	339
0.4-0.5	76
0.5-0.6	17
0.6-0.7	11
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	1
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC470214
0.9149	High Similarity	NPC109371
0.8723	High Similarity	NPC63345
0.74	Intermediate Similarity	NPC86198
0.6727	Remote Similarity	NPC200988
0.6727	Remote Similarity	NPC145023
0.66	Remote Similarity	NPC70084
0.6364	Remote Similarity	NPC25689
0.6349	Remote Similarity	NPC79715
0.6349	Remote Similarity	NPC108659
0.6296	Remote Similarity	NPC265454
0.6	Remote Similarity	NPC610
0.6	Remote Similarity	NPC179002
0.6	Remote Similarity	NPC257430
0.6	Remote Similarity	NPC175799
0.5714	Remote Similarity	NPC231607
0.5556	Remote Similarity	NPC34634
0.5455	Remote Similarity	NPC226401
0.5455	Remote Similarity	NPC158325
0.5455	Remote Similarity	NPC174096
0.5455	Remote Similarity	NPC193018
0.5397	Remote Similarity	NPC160854
0.5397	Remote Similarity	NPC469704
0.5397	Remote Similarity	NPC469703
0.5273	Remote Similarity	NPC75039
0.5273	Remote Similarity	NPC98305
0.52	Remote Similarity	NPC187583
0.5185	Remote Similarity	NPC177576
0.5085	Remote Similarity	NPC153795
0.5085	Remote Similarity	NPC42911
0.5079	Remote Similarity	NPC135464
0.5079	Remote Similarity	NPC92623

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC470215 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3131
0.1-0.2	5729
0.2-0.3	269
0.3-0.4	21
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