NPASS Compound

Natural Product: NPC221862

Natural Product ID	NPC221862
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	PVXPPJIGRGXGCY-IPFGBZKGSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	10125936
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0004603] Organic oxygen compounds [CHEMONTID:0000323] Organooxygen compounds [CHEMONTID:0000011] Carbohydrates and carbohydrate conjugates [CHEMONTID:0002105] Glycosyl compounds [CHEMONTID:0002207] O-glycosyl compounds

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 45 46 0 0 0 0 0 0 0 0999 V2000 4.5412 -1.3448 0.9190 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5402 -0.5347 0.0827 C 0 0 2 0 0 0 0 0 0 0 0 0 4.2993 0.6862 -0.3920 C 0 0 2 0 0 0 0 0 0 0 0 0 3.3579 1.8567 -0.6110 C 0 0 1 0 0 0 0 0 0 0 0 0 1.9707 1.2989 -0.8777 C 0 0 2 0 0 0 0 0 0 0 0 0 1.5076 0.5775 0.3440 C 0 0 1 0 0 0 0 0 0 0 0 0 0.3730 -0.2225 0.0794 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6850 0.2022 0.8396 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9393 -0.5799 0.6351 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.3965 -0.5925 -0.8080 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.8771 -0.8575 -0.6170 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.1358 -0.1497 0.6871 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.2463 -0.8015 1.4763 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4625 -0.0317 2.6195 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5833 1.1524 0.3649 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9772 -0.1343 1.4057 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6319 -0.3199 -1.6576 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7754 -1.5984 -1.5387 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4709 -0.2250 0.8771 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0318 0.4712 -2.0096 O 0 0 0 0 0 0 0 0 0 0 0 0 3.3308 2.6736 0.5019 O 0 0 0 0 0 0 0 0 0 0 0 0 4.8618 0.3743 -1.6271 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9176 -0.5197 1.9949 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0992 -2.2911 1.2673 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4193 -1.5112 0.2383 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2446 -1.1123 -0.8067 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1298 0.9523 0.2941 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6465 2.4420 -1.5005 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3347 2.1850 -1.0945 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2225 1.3391 1.1055 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3980 0.1049 1.9067 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9344 1.2804 0.6153 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7743 -1.6644 0.9045 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3004 0.4090 -1.2829 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0649 -1.9427 -0.4835 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9155 -1.8069 1.8014 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1681 -0.9169 0.8747 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9529 0.8102 2.4106 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1953 1.0369 -0.4050 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2542 -1.0300 -1.9534 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4335 -2.3593 -1.5843 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6592 0.9414 -2.8126 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3054 2.1105 1.2983 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8228 0.6742 -1.6799 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0152 -1.0320 2.8360 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 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 12 15 1 6 12 16 1 0 11 17 1 0 10 18 1 0 6 19 1 0 5 20 1 0 4 21 1 0 3 22 1 0 1 23 1 0 19 2 1 0 16 9 1 0 1 24 1 0 1 25 1 0 2 26 1 6 3 27 1 1 4 28 1 6 5 29 1 6 6 30 1 1 8 31 1 0 8 32 1 0 9 33 1 1 10 34 1 6 11 35 1 1 13 36 1 0 13 37 1 0 14 38 1 0 15 39 1 0 17 40 1 0 18 41 1 0 20 42 1 0 21 43 1 0 22 44 1 0 23 45 1 0 M END

Standard InCHIKey	PVXPPJIGRGXGCY-IPFGBZKGSA-N
Standard InCHI	InChI=1S/C12H22O11/c13-1-4-6(15)8(17)9(18)11(22-4)21-2-5-7(16)10(19)12(20,3-14)23-5/h4-11,13-20H,1-3H2/t4-,5-,6-,7-,8+,9-,10+,11+,12-/m1/s1
SMILES	C([C@@H]1[C@H]([C@@H]([C@H]([C@@H](OC[C@@H]2[C@H]([C@@H]([C@](CO)(O)O2)O)O)O1)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	342.12	Volume:	295.688 ? Van der Waals volume.
Dense:	1.157	LogP:	-2.38 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	-1.516 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-0.025 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	11.0
TPSA:	189.53 ? Topological Polar Surface Area.	H-Bond Acceptor:	11.0
H-Bond Donor:	8.0	Rings:	2.0
Heavy Atoms:	11.0

MedChem Properties

QED Drug-Likeness Score:	0.238	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.487	Fsp³:	1.0
MCE-18:	46.75 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.095	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.11 ? 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:	0.428	Promiscuous compounds:	0.074

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.799	MDCK Permeability:	-4.95
Pgp-inhibitor:	0.0	Pgp-substrate:	0.826
PAMPA:	1.0 ? 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):	0.999
20% Bioavailability (F20%):	0.954	30% Bioavailability (F30%):	0.999
50% Bioavailability (F50%):	0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.128	MRP1:	0.032
Plasma Protein Binding (PPB):	30.182%	Volume Distribution (VD):	-0.445
Fu:	78.335% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.992
OATP1B3 inhibitor:	0.992	BCRP inhibitor:	0.045
BSEP inhibitor:	0.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.004
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.62
HLM stability:	0.001 ? 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):

1.492

Half-life (T1/2):

2.045

ADMET: Toxicity

hERG Blockers:	0.004	hERG Blockers (10um):	0.056
Human Hepatotoxicity (H-HT):	0.552	Drug-induced Liver Injury (DILI):	0.326
AMES Toxicity:	0.925	Rat Oral Acute Toxicity:	0.022
Maximum Recommended Daily Dose:	0.004	Skin Sensitization:	0.999
Carcinogencity:	0.354	Eye Corrosion:	0.0
Eye Irritation:	0.783	Respiratory Toxicity:	0.008
Drug-induced Neurotoxicity:	0.013	Ototoxicity:	0.845
Hematotoxicity:	0.262	Drug-induced Nephrotoxicity:	0.805
Genotoxicity:	0.415	RPMI-8226 Immunitoxicity:	0.14
A549 Cytotoxicity:	0.212	Hek293 Cytotoxicity:	0.092
BCF:	0.14 ? 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:	1.634 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	3.055 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	2.223 ? 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
NPO29463	Pogostemon cablin	Species	Lamiaceae	Eukaryota	n.a.	leaf	n.a.	PMID[12575075]
NPO29463	Pogostemon cablin	Species	Lamiaceae	Eukaryota	n.a.	stem	n.a.	PMID[12575075]
NPO29463	Pogostemon cablin	Species	Lamiaceae	Eukaryota	n.a.	whole plant	n.a.	PMID[15577255]
NPO29463	Pogostemon cablin	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[30188125]
NPO29463	Pogostemon cablin	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO29463	Pogostemon cablin	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO29463	Pogostemon cablin	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO29463	Pogostemon cablin	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO29463	Pogostemon cablin	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO29463	Pogostemon cablin	Species	Lamiaceae	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

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 NPC221862 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	33019
0.1-0.2	13180
0.2-0.3	3024
0.3-0.4	551
0.4-0.5	61
0.5-0.6	19
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	Natural Product ID
0.6279	Remote Similarity	NPC145112
0.5897	Remote Similarity	NPC124963
0.587	Remote Similarity	NPC89145
0.587	Remote Similarity	NPC157514
0.587	Remote Similarity	NPC322314
0.587	Remote Similarity	NPC269166
0.575	Remote Similarity	NPC326533
0.5641	Remote Similarity	NPC323574
0.551	Remote Similarity	NPC147292
0.5294	Remote Similarity	NPC34877
0.5227	Remote Similarity	NPC233726
0.5217	Remote Similarity	NPC323361
0.5128	Remote Similarity	NPC42503
0.5128	Remote Similarity	NPC282143
0.5128	Remote Similarity	NPC107914
0.5128	Remote Similarity	NPC242073
0.5128	Remote Similarity	NPC299781
0.5128	Remote Similarity	NPC157193
0.5128	Remote Similarity	NPC608193
0.5094	Remote Similarity	NPC12040

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC221862 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	8047
0.1-0.2	986
0.2-0.3	91
0.3-0.4	10
0.4-0.5	12
0.5-0.6	4
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
0.54	Remote Similarity	NPD3181	Phase 3
0.5227	Remote Similarity	NPD904	Phase 3
0.5217	Remote Similarity	NPD889	Approved
0.5217	Remote Similarity	NPD894	Phase 4

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