NPASS Compound

Natural Product: NPC95407

Natural Product ID	NPC95407
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	GTLGHKNKLRZSMO-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	3016110
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 30 30 0 0 0 0 0 0 0 0999 V2000 -4.0301 1.4130 -0.9044 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1479 0.8714 0.1812 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8169 0.3604 -0.3750 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0329 -0.1519 0.8119 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2949 -0.6828 0.4081 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4191 -2.0143 0.0717 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6422 -2.5466 -0.3102 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7424 -1.7037 -0.3459 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6565 -0.3640 -0.0157 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4112 0.1198 0.3596 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7926 0.3971 -0.0780 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9022 1.7543 0.2150 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9685 -2.2269 -0.7264 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7948 -0.1761 0.8413 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6236 0.6400 -1.4119 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3832 1.9395 -1.6352 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7494 2.1223 -0.4350 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9696 1.6786 0.9180 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3155 1.1538 -0.9271 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0800 -0.4642 -1.0766 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9603 0.6617 1.5540 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6588 -0.9481 1.2896 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4354 -2.6769 0.0976 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6993 -3.5981 -0.5672 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3534 1.1636 0.6150 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8830 1.9560 0.7346 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1143 2.1663 0.8498 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0067 2.2965 -0.7677 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6270 -2.5705 -0.0408 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5149 -0.5701 0.2788 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 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 2 0 9 11 1 0 11 12 1 0 8 13 1 0 2 14 1 0 10 5 1 0 1 15 1 0 1 16 1 0 1 17 1 0 2 18 1 0 3 19 1 0 3 20 1 0 4 21 1 0 4 22 1 0 6 23 1 0 7 24 1 0 10 25 1 0 12 26 1 0 12 27 1 0 12 28 1 0 13 29 1 0 14 30 1 0 M END

Standard InCHIKey	GTLGHKNKLRZSMO-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C11H16O3/c1-8(12)3-4-9-5-6-10(13)11(7-9)14-2/h5-8,12-13H,3-4H2,1-2H3
SMILES	CC(CCc1ccc(c(c1)OC)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	196.11	Volume:	208.717 ? Van der Waals volume.
Dense:	0.94	LogP:	1.676 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.563 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.37 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	6.0
TPSA:	49.69 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	2.0	Rings:	1.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.77	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.313	Fsp³:	0.455
MCE-18:	14.0 ? 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:	0.081	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.017 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.033 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.79	Promiscuous compounds:	0.736

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.734	MDCK Permeability:	-4.654
Pgp-inhibitor:	0.222	Pgp-substrate:	0.553
PAMPA:	0.11 ? 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):	0.111
20% Bioavailability (F20%):	0.371	30% Bioavailability (F30%):	0.48
50% Bioavailability (F50%):	0.915

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.021	MRP1:	0.686
Plasma Protein Binding (PPB):	48.678%	Volume Distribution (VD):	-0.349
Fu:	47.133% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.936
OATP1B3 inhibitor:	0.938	BCRP inhibitor:	0.332
BSEP inhibitor:	0.876

ADMET: Metabolism

CYP1A2-inhibitor:	0.906	CYP1A2-substrate:	0.039
CYP2C19-inhibitor:	0.997	CYP2C19-substrate:	0.002
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	0.007
CYP2D6-inhibitor:	0.882	CYP2D6-substrate:	0.11
CYP3A4-inhibitor:	0.979	CYP3A4-substrate:	0.014
CYP2B6-substrate:	0.044	CYP2C8-inhibitor:	0.982
HLM stability:	0.084 ? 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):

9.048

Half-life (T1/2):

1.352

ADMET: Toxicity

hERG Blockers:	0.193	hERG Blockers (10um):	0.673
Human Hepatotoxicity (H-HT):	0.45	Drug-induced Liver Injury (DILI):	0.072
AMES Toxicity:	0.323	Rat Oral Acute Toxicity:	0.098
Maximum Recommended Daily Dose:	0.233	Skin Sensitization:	0.608
Carcinogencity:	0.344	Eye Corrosion:	0.799
Eye Irritation:	0.987	Respiratory Toxicity:	0.489
Drug-induced Neurotoxicity:	0.198	Ototoxicity:	0.559
Hematotoxicity:	0.227	Drug-induced Nephrotoxicity:	0.297
Genotoxicity:	0.016	RPMI-8226 Immunitoxicity:	0.056
A549 Cytotoxicity:	0.145	Hek293 Cytotoxicity:	0.183
BCF:	0.339 ? 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:	2.754 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.034 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.249 ? 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

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

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 NPC95407 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	15863
0.1-0.2	25558
0.2-0.3	7299
0.3-0.4	818
0.4-0.5	206
0.5-0.6	69
0.6-0.7	28
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
0.7949	Intermediate Similarity	NPC312675
0.7949	Intermediate Similarity	NPC262156
0.7949	Intermediate Similarity	NPC184651
0.7949	Intermediate Similarity	NPC113865
0.7778	Intermediate Similarity	NPC8547
0.7273	Intermediate Similarity	NPC164386
0.7209	Intermediate Similarity	NPC473853
0.7209	Intermediate Similarity	NPC98631
0.7209	Intermediate Similarity	NPC206615
0.7209	Intermediate Similarity	NPC470212
0.7045	Intermediate Similarity	NPC324571
0.7	Intermediate Similarity	NPC17943
0.7	Intermediate Similarity	NPC299406
0.6957	Remote Similarity	NPC311595
0.6957	Remote Similarity	NPC24474
0.6944	Remote Similarity	NPC156840
0.6889	Remote Similarity	NPC343720
0.6889	Remote Similarity	NPC54872
0.6739	Remote Similarity	NPC137427
0.6667	Remote Similarity	NPC471693
0.65	Remote Similarity	NPC255675
0.6444	Remote Similarity	NPC481914
0.641	Remote Similarity	NPC221049
0.6364	Remote Similarity	NPC51840
0.6364	Remote Similarity	NPC82679
0.6327	Remote Similarity	NPC310718
0.6279	Remote Similarity	NPC177291
0.6279	Remote Similarity	NPC127937
0.625	Remote Similarity	NPC165133
0.625	Remote Similarity	NPC242885
0.625	Remote Similarity	NPC95614
0.625	Remote Similarity	NPC232316
0.62	Remote Similarity	NPC215941
0.62	Remote Similarity	NPC123196
0.62	Remote Similarity	NPC311419
0.6154	Remote Similarity	NPC257124
0.6087	Remote Similarity	NPC74817
0.6078	Remote Similarity	NPC275724
0.6078	Remote Similarity	NPC244246
0.6078	Remote Similarity	NPC611247
0.6	Remote Similarity	NPC140359
0.5962	Remote Similarity	NPC65935
0.5962	Remote Similarity	NPC319282
0.5957	Remote Similarity	NPC311680
0.5957	Remote Similarity	NPC114298
0.5957	Remote Similarity	NPC212015
0.5957	Remote Similarity	NPC159968
0.5957	Remote Similarity	NPC606450
0.5952	Remote Similarity	NPC85488
0.5918	Remote Similarity	NPC481913
0.5882	Remote Similarity	NPC20287
0.5882	Remote Similarity	NPC20404
0.5854	Remote Similarity	NPC193544
0.5849	Remote Similarity	NPC207613
0.5833	Remote Similarity	NPC282000
0.5833	Remote Similarity	NPC4181
0.5833	Remote Similarity	NPC201777
0.5833	Remote Similarity	NPC303680
0.5833	Remote Similarity	NPC604524
0.5778	Remote Similarity	NPC487676
0.5769	Remote Similarity	NPC12022
0.5769	Remote Similarity	NPC278308
0.5745	Remote Similarity	NPC5018
0.5625	Remote Similarity	NPC53305
0.56	Remote Similarity	NPC164778
0.56	Remote Similarity	NPC163083
0.5581	Remote Similarity	NPC57490
0.5581	Remote Similarity	NPC603326
0.5581	Remote Similarity	NPC603989
0.5532	Remote Similarity	NPC186843
0.5526	Remote Similarity	NPC138117
0.5526	Remote Similarity	NPC325292
0.549	Remote Similarity	NPC257976
0.549	Remote Similarity	NPC273686
0.549	Remote Similarity	NPC242372
0.549	Remote Similarity	NPC312404
0.5476	Remote Similarity	NPC181969
0.5455	Remote Similarity	NPC197757
0.5435	Remote Similarity	NPC117214
0.5435	Remote Similarity	NPC66518
0.5435	Remote Similarity	NPC56214
0.5435	Remote Similarity	NPC476968
0.54	Remote Similarity	NPC487210
0.5319	Remote Similarity	NPC227217
0.5319	Remote Similarity	NPC117780
0.5294	Remote Similarity	NPC123228
0.5294	Remote Similarity	NPC123722
0.5273	Remote Similarity	NPC252307
0.5273	Remote Similarity	NPC245826
0.5263	Remote Similarity	NPC7097
0.525	Remote Similarity	NPC293619
0.5217	Remote Similarity	NPC194416
0.5217	Remote Similarity	NPC31344
0.5217	Remote Similarity	NPC317769
0.5217	Remote Similarity	NPC203133
0.5208	Remote Similarity	NPC127587
0.5192	Remote Similarity	NPC179777
0.5192	Remote Similarity	NPC257589
0.5185	Remote Similarity	NPC84076
0.5185	Remote Similarity	NPC194519
0.5185	Remote Similarity	NPC280767
0.5122	Remote Similarity	NPC32163
0.5116	Remote Similarity	NPC16651
0.5102	Remote Similarity	NPC5428
0.5102	Remote Similarity	NPC607444
0.5098	Remote Similarity	NPC470213
0.5094	Remote Similarity	NPC276466
0.5094	Remote Similarity	NPC229497
0.5094	Remote Similarity	NPC231572
0.5082	Remote Similarity	NPC52277

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC95407 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	2928
0.1-0.2	5650
0.2-0.3	549
0.3-0.4	20
0.4-0.5	2
0.5-0.6	0
0.6-0.7	1
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
0.6154	Remote Similarity	NPD228	Phase 0

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