NPASS Compound

Natural Product: NPC66020

Natural Product ID	NPC66020
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(-)-1-P-Menthene-7,8-Diol
IUPAC Name	2-[(1S)-4-(hydroxymethyl)cyclohex-3-en-1-yl]propan-2-ol
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL448219
PubChem CID	44566704
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001549] Monoterpenoids [CHEMONTID:0001401] Menthane monoterpenoids

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 -2.2954 1.1788 -0.7182 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0676 0.0112 0.1703 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7686 -1.1747 -0.4383 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6188 -0.2611 0.4760 C 0 0 2 0 0 0 0 0 0 0 0 0 0.0406 0.9151 1.1681 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4442 0.4714 1.4767 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1530 0.0470 0.4352 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4726 0.0655 -0.8889 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1678 -0.6861 -0.7281 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5448 -0.4249 0.5510 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3584 0.3919 -0.2493 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7028 0.2676 1.3975 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6036 2.0070 -0.6261 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3088 0.8937 -1.8101 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3262 1.6031 -0.5381 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6411 -1.2229 -1.5399 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5264 -2.1262 0.0712 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8664 -1.0141 -0.2761 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5547 -1.1032 1.2125 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0281 1.8357 0.5819 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4501 1.0386 2.1732 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8705 0.4868 2.4677 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0673 -0.4946 -1.6441 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3182 1.1242 -1.1944 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3839 -0.5680 -1.6794 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4531 -1.7786 -0.6926 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8965 -0.4808 1.5873 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6684 -1.4591 0.1219 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1689 0.6858 0.2470 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5380 -0.2292 1.5044 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 1 0 7 10 1 0 10 11 1 0 2 12 1 0 9 4 1 0 1 13 1 0 1 14 1 0 1 15 1 0 3 16 1 0 3 17 1 0 3 18 1 0 4 19 1 1 5 20 1 0 5 21 1 0 6 22 1 0 8 23 1 0 8 24 1 0 9 25 1 0 9 26 1 0 10 27 1 0 10 28 1 0 11 29 1 0 12 30 1 0 M END

Standard InCHIKey	XYKGEKWHBMLSGS-SECBINFHSA-N
Standard InCHI	InChI=1S/C10H18O2/c1-10(2,12)9-5-3-8(7-11)4-6-9/h3,9,11-12H,4-7H2,1-2H3/t9-/m1/s1
SMILES	CC(C)([C@@H]1CC=C(CC1)CO)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	170.13	Volume:	187.904 ? Van der Waals volume.
Dense:	0.905	LogP:	1.758 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.815 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.555 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	6.0
TPSA:	40.46 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	2.0	Rings:	1.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.616	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.435	Fsp³:	0.8
MCE-18:	19.556 ? 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:	0	PAINS Alert:	0
Colloidal aggregators:	0.075	Fluc inhibitor:	0.11 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.005 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.982	Promiscuous compounds:	0.196

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.55	MDCK Permeability:	-4.618
Pgp-inhibitor:	0.046	Pgp-substrate:	0.232
PAMPA:	0.384 ? 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):	0.084
20% Bioavailability (F20%):	0.105	30% Bioavailability (F30%):	0.251
50% Bioavailability (F50%):	0.265

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.118	MRP1:	0.534
Plasma Protein Binding (PPB):	43.635%	Volume Distribution (VD):	-0.131
Fu:	57.198% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.82
OATP1B3 inhibitor:	0.895	BCRP inhibitor:	0.09
BSEP inhibitor:	0.261

ADMET: Metabolism

CYP1A2-inhibitor:	0.983	CYP1A2-substrate:	0.006
CYP2C19-inhibitor:	0.991	CYP2C19-substrate:	0.003
CYP2C9-inhibitor:	0.76	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.991	CYP2D6-substrate:	0.046
CYP3A4-inhibitor:	0.08	CYP3A4-substrate:	0.025
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.73
HLM stability:	0.115 ? 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):

9.185

Half-life (T1/2):

1.389

ADMET: Toxicity

hERG Blockers:	0.033	hERG Blockers (10um):	0.207
Human Hepatotoxicity (H-HT):	0.468	Drug-induced Liver Injury (DILI):	0.213
AMES Toxicity:	0.364	Rat Oral Acute Toxicity:	0.156
Maximum Recommended Daily Dose:	0.114	Skin Sensitization:	0.672
Carcinogencity:	0.775	Eye Corrosion:	0.821
Eye Irritation:	0.984	Respiratory Toxicity:	0.471
Drug-induced Neurotoxicity:	0.2	Ototoxicity:	0.414
Hematotoxicity:	0.349	Drug-induced Nephrotoxicity:	0.198
Genotoxicity:	0.042	RPMI-8226 Immunitoxicity:	0.038
A549 Cytotoxicity:	0.077	Hek293 Cytotoxicity:	0.059
BCF:	0.443 ? 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:	2.468 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.044 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	2.991 ? 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
NPO9798	Paeonia lactiflora	Species	Paeoniaceae	Eukaryota	Seeds	Henan province, China		DOI[10.1016/j.foodres.2020.109416]
NPO9798	Paeonia lactiflora	Species	Paeoniaceae	Eukaryota	Seeds	Gansu province, China		DOI[10.1016/j.foodres.2020.109416]
NPO9798	Paeonia lactiflora	Species	Paeoniaceae	Eukaryota	Seeds	Anhui province, China		DOI[10.1016/j.foodres.2020.109416]
NPO9798	Paeonia lactiflora	Species	Paeoniaceae	Eukaryota	Seeds	Shanxi province, China		DOI[10.1016/j.foodres.2020.109416]
NPO9798	Paeonia lactiflora	Species	Paeoniaceae	Eukaryota	Seeds	Shandong province, China		DOI[10.1016/j.foodres.2020.109416]
NPO9798	Paeonia lactiflora	Species	Paeoniaceae	Eukaryota	n.a.	root	n.a.	DOI[10.2174/092986712800229032]
NPO7630	Cyperus longus	Species	Cyperaceae	Eukaryota	n.a.	Egyptian herbal medicine	n.a.	PMID[15104485]
NPO9798	Paeonia lactiflora	Species	Paeoniaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19402674]
NPO9798	Paeonia lactiflora	Species	Paeoniaceae	Eukaryota	n.a.	root	n.a.	PMID[19721258]
NPO9798	Paeonia lactiflora	Species	Paeoniaceae	Eukaryota	n.a.	root	n.a.	PMID[19772486]
NPO9798	Paeonia lactiflora	Species	Paeoniaceae	Eukaryota	Roots	n.a.	n.a.	PMID[20806783]
NPO9798	Paeonia lactiflora	Species	Paeoniaceae	Eukaryota	n.a.	root	n.a.	PMID[21782011]
NPO9798	Paeonia lactiflora	Species	Paeoniaceae	Eukaryota	n.a.	root	n.a.	PMID[22190295]
NPO9798	Paeonia lactiflora	Species	Paeoniaceae	Eukaryota	n.a.	seed	n.a.	PMID[23497864]
NPO9798	Paeonia lactiflora	Species	Paeoniaceae	Eukaryota	n.a.	root	n.a.	PMID[26838074]
NPO9798	Paeonia lactiflora	Species	Paeoniaceae	Eukaryota	n.a.	root	n.a.	PMID[27313650]
NPO9798	Paeonia lactiflora	Species	Paeoniaceae	Eukaryota	n.a.	root	n.a.	PMID[27429639]
NPO9798	Paeonia lactiflora	Species	Paeoniaceae	Eukaryota	Roots	n.a.	n.a.	PMID[29741372]
NPO9798	Paeonia lactiflora	Species	Paeoniaceae	Eukaryota	Seeds	HeZe, ShanDong, China	early autumn (from August to the beginning of September	PMID[32545196]
NPO9798	Paeonia lactiflora	Species	Paeoniaceae	Eukaryota	Roots	n.a.	n.a.	PMID[32951423]
NPO9798	Paeonia lactiflora	Species	Paeoniaceae	Eukaryota	Seeds	Xinjiang,China		PMID[33063333]
NPO7630	Cyperus longus	Species	Cyperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO9798	Paeonia lactiflora	Species	Paeoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO9798	Paeonia lactiflora	Species	Paeoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO9798	Paeonia lactiflora	Species	Paeoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO9798	Paeonia lactiflora	Species	Paeoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO9798	Paeonia lactiflora	Species	Paeoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO7630	Cyperus longus	Species	Cyperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9798	Paeonia lactiflora	Species	Paeoniaceae	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	2
Inhibition	4

Activity Type	# Activity
Individual protein	1
Cell line	5

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT203	Individual protein	Carboxylesterase 2	Homo sapiens	IC50	=	1900.0	nM	PMID[32951423]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT993	Cell line	Hepatocyte	Mus musculus	IC50	=	90000.0	nM	PMID[10924160]
NPT993	Cell line	Hepatocyte	Mus musculus	Inhibition	=	53.3	%	PMID[10924160]
NPT993	Cell line	Hepatocyte	Mus musculus	Inhibition	=	16.7	%	PMID[10924160]
NPT993	Cell line	Hepatocyte	Mus musculus	Inhibition	=	1.7	%	PMID[21970540]
NPT993	Cell line	Hepatocyte	Mus musculus	Inhibition	=	-1.5	%	PMID[21970540]

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 NPC66020 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	26382
0.1-0.2	21702
0.2-0.3	1668
0.3-0.4	88
0.4-0.5	11
0.5-0.6	2
0.6-0.7	5
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
0.68	Remote Similarity	NPC26906
0.68	Remote Similarity	NPC214584
0.6296	Remote Similarity	NPC148216
0.6296	Remote Similarity	NPC130209
0.6296	Remote Similarity	NPC148163
0.5484	Remote Similarity	NPC329773
0.5294	Remote Similarity	NPC136813

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC66020 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7855
0.1-0.2	1226
0.2-0.3	63
0.3-0.4	4
0.4-0.5	1
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
0.6296	Remote Similarity	NPD342	Phase 1

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