NPASS Compound

Natural Product: NPC181969

Natural Product ID	NPC181969
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(1R,2S)-1-(4-Hydroxy-3-Methoxyphenyl)Propane-1,2-Diol
IUPAC Name	(1R,2S)-1-(4-hydroxy-3-methoxyphenyl)propane-1,2-diol
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1682391
PubChem CID	53320292
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0002448] Benzenoids [CHEMONTID:0000134] Phenols [CHEMONTID:0000190] Methoxyphenols

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 28 28 0 0 0 0 0 0 0 0999 V2000 -1.3991 1.5902 1.7116 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8752 0.1790 1.5266 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.9607 -0.1566 0.0796 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.6824 -0.2883 -0.6230 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7376 -0.8365 -1.9066 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4141 -1.0030 -2.6457 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6358 -0.6374 -2.1437 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7085 -0.0968 -0.8833 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5485 0.0610 -0.1623 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9123 0.2922 -0.3207 O 0 0 0 0 0 0 0 0 0 0 0 0 2.9663 0.8458 0.9763 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8276 -0.7856 -2.8515 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6279 -1.3932 -0.0891 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1676 -0.7631 2.2661 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1336 2.0977 0.7456 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5944 1.7040 2.4627 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2340 2.2421 2.1119 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9342 0.1073 1.9301 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5974 0.5944 -0.4174 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6691 -1.1391 -2.3458 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3814 -1.4290 -3.6461 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6218 0.4785 0.8118 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4761 1.8424 0.9654 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4348 0.1897 1.7048 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0366 0.9394 1.2486 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3208 -1.6651 -2.7635 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4329 -1.3491 0.4624 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2382 -1.6208 1.7950 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 2 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 7 12 1 0 3 13 1 0 2 14 1 0 9 4 1 0 1 15 1 0 1 16 1 0 1 17 1 0 2 18 1 1 3 19 1 6 5 20 1 0 6 21 1 0 9 22 1 0 11 23 1 0 11 24 1 0 11 25 1 0 12 26 1 0 13 27 1 0 14 28 1 0 M END

Standard InCHIKey	PZKYCBMLUGVAGH-WKEGUHRASA-N
Standard InCHI	InChI=1S/C10H14O4/c1-6(11)10(13)7-3-4-8(12)9(5-7)14-2/h3-6,10-13H,1-2H3/t6-,10-/m0/s1
SMILES	C[C@@H]([C@@H](c1ccc(c(c1)OC)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	198.09	Volume:	200.211 ? Van der Waals volume.
Dense:	0.989	LogP:	0.056 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.327 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-0.858 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	6.0
TPSA:	69.92 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	3.0	Rings:	1.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.672	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.81	Fsp³:	0.4
MCE-18:	16.0 ? 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:	Accepted	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.339	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.028 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.074 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.647	Promiscuous compounds:	0.732

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.95	MDCK Permeability:	-4.701
Pgp-inhibitor:	0.0	Pgp-substrate:	0.349
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):	0.014
20% Bioavailability (F20%):	0.198	30% Bioavailability (F30%):	0.282
50% Bioavailability (F50%):	0.916

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.014	MRP1:	0.714
Plasma Protein Binding (PPB):	35.819%	Volume Distribution (VD):	0.024
Fu:	61.979% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.942
OATP1B3 inhibitor:	0.994	BCRP inhibitor:	0.386
BSEP inhibitor:	0.038

ADMET: Metabolism

CYP1A2-inhibitor:	0.449	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.275	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.003	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.347	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.001
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.046
HLM stability:	0.556 ? 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):

7.329

Half-life (T1/2):

2.38

ADMET: Toxicity

hERG Blockers:	0.054	hERG Blockers (10um):	0.464
Human Hepatotoxicity (H-HT):	0.58	Drug-induced Liver Injury (DILI):	0.037
AMES Toxicity:	0.506	Rat Oral Acute Toxicity:	0.136
Maximum Recommended Daily Dose:	0.194	Skin Sensitization:	0.741
Carcinogencity:	0.238	Eye Corrosion:	0.066
Eye Irritation:	0.952	Respiratory Toxicity:	0.11
Drug-induced Neurotoxicity:	0.261	Ototoxicity:	0.432
Hematotoxicity:	0.071	Drug-induced Nephrotoxicity:	0.158
Genotoxicity:	0.161	RPMI-8226 Immunitoxicity:	0.082
A549 Cytotoxicity:	0.276	Hek293 Cytotoxicity:	0.205
BCF:	0.386 ? 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:	2.336 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	3.553 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	2.832 ? 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
NPO20553	Zingiber officinale	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1016/j.jarmap.2018.11.004]
NPO20553	Zingiber officinale	Species	Zingiberaceae	Eukaryota	rhizomes	n.a.	n.a.	PMID[18177011]
NPO20553	Zingiber officinale	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19271742]
NPO20553	Zingiber officinale	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[20590154]
NPO20553	Zingiber officinale	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[32872604]
NPO20553	Zingiber officinale	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[36352904]
NPO20553	Zingiber officinale	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[39679248]
NPO20553	Zingiber officinale	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[39680258]
NPO20553	Zingiber officinale	Species	Zingiberaceae	Eukaryota	n.a.	rhizome	n.a.	PMID[8064299]
NPO20553	Zingiber officinale	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[8064299]
NPO20553	Zingiber officinale	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO20553	Zingiber officinale	Species	Zingiberaceae	Eukaryota	Resin, Exudate, Sap	n.a.	n.a.	Database[FooDB]
NPO20553	Zingiber officinale	Species	Zingiberaceae	Eukaryota	n.a.	n.a.		Database[FooDB]
NPO20553	Zingiber officinale	Species	Zingiberaceae	Eukaryota	Root	n.a.	n.a.	Database[FooDB]
NPO20553	Zingiber officinale	Species	Zingiberaceae	Eukaryota	Rhizome	n.a.	n.a.	Database[FooDB]
NPO20553	Zingiber officinale	Species	Zingiberaceae	Eukaryota	Plant	n.a.	n.a.	Database[FooDB]
NPO20553	Zingiber officinale	Species	Zingiberaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO20553	Zingiber officinale	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO20553	Zingiber officinale	Species	Zingiberaceae	Eukaryota	n.a.	n.a.		Database[Phenol-Explorer]
NPO20553	Zingiber officinale	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO20553	Zingiber officinale	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO20553	Zingiber officinale	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]

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	1

Activity Type	# Activity
Individual protein	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1120	Individual protein	Pancreatic triacylglycerol lipase	Sus scrofa	IC50	=	12100.0	nM	PMID[21282056]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

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 NPC181969 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	20745
0.1-0.2	22571
0.2-0.3	5716
0.3-0.4	610
0.4-0.5	166
0.5-0.6	35
0.6-0.7	6
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
0.7778	Intermediate Similarity	NPC35071
0.7778	Intermediate Similarity	NPC177475
0.7778	Intermediate Similarity	NPC148615
0.6944	Remote Similarity	NPC320987
0.6757	Remote Similarity	NPC326599
0.6757	Remote Similarity	NPC329595
0.65	Remote Similarity	NPC195292
0.641	Remote Similarity	NPC476343
0.6042	Remote Similarity	NPC480703
0.5952	Remote Similarity	NPC165045
0.5952	Remote Similarity	NPC118533
0.5714	Remote Similarity	NPC7097
0.5676	Remote Similarity	NPC156840
0.5676	Remote Similarity	NPC203719
0.5526	Remote Similarity	NPC32163
0.55	Remote Similarity	NPC471693
0.549	Remote Similarity	NPC601893
0.5455	Remote Similarity	NPC476968
0.5366	Remote Similarity	NPC255675
0.5263	Remote Similarity	NPC246358
0.5263	Remote Similarity	NPC293619
0.525	Remote Similarity	NPC160380
0.525	Remote Similarity	NPC38996
0.525	Remote Similarity	NPC8547
0.525	Remote Similarity	NPC221049
0.525	Remote Similarity	NPC36108
0.525	Remote Similarity	NPC140359
0.525	Remote Similarity	NPC233731
0.525	Remote Similarity	NPC610203
0.5208	Remote Similarity	NPC470990
0.52	Remote Similarity	NPC92164
0.5135	Remote Similarity	NPC251306
0.5128	Remote Similarity	NPC309203
0.5128	Remote Similarity	NPC604189
0.5122	Remote Similarity	NPC165133
0.5122	Remote Similarity	NPC242885
0.5122	Remote Similarity	NPC16651
0.5122	Remote Similarity	NPC139519
0.5122	Remote Similarity	NPC95614
0.5122	Remote Similarity	NPC232316
0.5116	Remote Similarity	NPC325625
0.5102	Remote Similarity	NPC310854
0.5098	Remote Similarity	NPC9370
0.5098	Remote Similarity	NPC287495

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC181969 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3805
0.1-0.2	4953
0.2-0.3	360
0.3-0.4	27
0.4-0.5	4
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