NPASS Compound

Natural Product: NPC275625

Natural Product ID	NPC275625
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	DWQIEUYIJNZWSH-QEEYODRMSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	57339442
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000279] Alkaloids and derivatives [CHEMONTID:0000058] Morphinans

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 48 51 0 0 0 0 0 0 0 0999 V2000 4.4529 2.1480 0.3293 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0287 1.1034 1.2785 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8352 0.8813 2.2411 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8203 0.3277 1.2242 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5795 -0.6413 2.1956 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4333 -1.3812 2.1292 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5036 -1.1728 1.0964 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6952 -2.0547 1.1298 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7588 -1.6867 0.1559 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.6646 -0.2750 -0.3135 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.9795 0.7226 0.7157 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5933 1.9708 0.5569 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8583 2.3633 -0.6305 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6052 3.5632 -0.8869 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3893 1.2961 -1.5767 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2701 -0.0407 -0.9275 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.1118 -1.0535 -2.0459 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4160 -2.4569 -1.6592 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7149 -2.5384 -1.0187 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.0820 -3.8996 -0.7293 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7122 -0.2210 0.1204 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8969 0.5178 0.2197 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0728 1.4536 -0.7667 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8697 2.9620 1.5116 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1006 3.6939 1.3932 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3138 1.8406 -0.7266 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5389 2.4273 0.5033 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9195 3.1109 0.5402 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3272 -0.7570 2.9637 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2722 -2.1240 2.8933 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0736 -2.0148 2.1807 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3523 -3.0966 0.9768 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7564 -1.8338 0.6280 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3660 -0.1702 -1.1925 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5259 0.4785 1.6195 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3893 1.6031 -2.2585 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3015 1.1796 -2.2619 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9663 -0.9872 -2.3689 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7084 -0.7045 -2.9018 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4910 -3.0532 -2.5920 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3842 -2.9096 -1.0575 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5024 -4.5417 -1.4545 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1463 -4.0376 -1.0131 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9318 -4.2040 0.3063 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9928 2.4285 -0.6247 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1887 4.4372 2.2048 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9630 3.0420 1.2657 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0235 4.3041 0.4457 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 2 4 1 0 4 5 2 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 13 15 1 0 16 15 1 6 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 16 21 1 0 21 22 2 0 22 23 1 0 12 24 1 0 24 25 1 0 22 4 1 0 21 7 1 0 19 9 1 0 16 10 1 0 1 26 1 0 1 27 1 0 1 28 1 0 5 29 1 0 6 30 1 0 8 31 1 0 8 32 1 0 9 33 1 1 10 34 1 6 11 35 1 0 15 36 1 0 15 37 1 0 17 38 1 0 17 39 1 0 18 40 1 0 18 41 1 0 20 42 1 0 20 43 1 0 20 44 1 0 23 45 1 0 25 46 1 0 25 47 1 0 25 48 1 0 M END

Standard InCHIKey	DWQIEUYIJNZWSH-QEEYODRMSA-N
Standard InCHI	InChI=1S/C20H23NO4/c1-11(22)13-5-4-12-8-15-14-9-17(25-3)16(23)10-20(14,6-7-21(15)2)18(12)19(13)24/h4-5,9,14-15,24H,6-8,10H2,1-3H3/t14-,15+,20-/m1/s1
SMILES	CC(=O)c1ccc2C[C@H]3[C@H]4C=C(C(=O)C[C@@]4(CCN3C)c2c1O)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	341.16	Volume:	350.589 ? Van der Waals volume.
Dense:	0.973	LogP:	1.692 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.793 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.649 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	22.0
TPSA:	66.84 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	1.0	Rings:	4.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.836	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.615	Fsp³:	0.5
MCE-18:	86.667 ? 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:	0	PAINS Alert:	0
Colloidal aggregators:	0.328	Fluc inhibitor:	0.048 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.353 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.09 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.005	Promiscuous compounds:	0.128

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.215	MDCK Permeability:	-4.89
Pgp-inhibitor:	0.004	Pgp-substrate:	0.526
PAMPA:	0.021 ? 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):	0.001
20% Bioavailability (F20%):	0.062	30% Bioavailability (F30%):	0.258
50% Bioavailability (F50%):	0.992

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.895	MRP1:	0.942
Plasma Protein Binding (PPB):	55.619%	Volume Distribution (VD):	0.176
Fu:	46.565% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.775
OATP1B3 inhibitor:	0.551	BCRP inhibitor:	0.005
BSEP inhibitor:	0.028

ADMET: Metabolism

CYP1A2-inhibitor:	0.712	CYP1A2-substrate:	0.129
CYP2C19-inhibitor:	0.229	CYP2C19-substrate:	0.019
CYP2C9-inhibitor:	0.025	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.073	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.816	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.037
HLM stability:	0.708 ? 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):

13.811

Half-life (T1/2):

2.238

ADMET: Toxicity

hERG Blockers:	0.165	hERG Blockers (10um):	0.479
Human Hepatotoxicity (H-HT):	0.695	Drug-induced Liver Injury (DILI):	0.332
AMES Toxicity:	0.718	Rat Oral Acute Toxicity:	0.699
Maximum Recommended Daily Dose:	0.803	Skin Sensitization:	0.834
Carcinogencity:	0.663	Eye Corrosion:	0.002
Eye Irritation:	0.439	Respiratory Toxicity:	0.896
Drug-induced Neurotoxicity:	0.748	Ototoxicity:	0.443
Hematotoxicity:	0.644	Drug-induced Nephrotoxicity:	0.69
Genotoxicity:	0.98	RPMI-8226 Immunitoxicity:	0.174
A549 Cytotoxicity:	0.299	Hek293 Cytotoxicity:	0.347
BCF:	0.852 ? 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:	3.734 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.852 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.307 ? 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
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.3987/COM-96-7609.]
NPO20526	Menispermum dauricum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11473438]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16038566]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	stem	n.a.	PMID[16964757]
NPO6328	Corydalis incisa	Species	Papaveraceae	Eukaryota	n.a.	aerial part	n.a.	PMID[17366734]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18081254]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	rhizome	n.a.	PMID[23059629]
NPO20526	Menispermum dauricum	Species	Menispermaceae	Eukaryota	n.a.	rhizome	n.a.	PMID[8281582]
NPO22500	Stephania dielsiana	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO20526	Menispermum dauricum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6328	Corydalis incisa	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28372	Corydalis pallida	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO6328	Corydalis incisa	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO28372	Corydalis pallida	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO20526	Menispermum dauricum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO22500	Stephania dielsiana	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO28372.1	Corydalis pallida var. tenuis	Varieties	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO28372.1	Corydalis pallida var. tenuis	Varieties	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO5493	Rhizoma menispermi	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[TCMID]
NPO22500	Stephania dielsiana	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO20526	Menispermum dauricum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO6328	Corydalis incisa	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO28372	Corydalis pallida	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO20526	Menispermum dauricum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO6328	Corydalis incisa	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO28372	Corydalis pallida	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28372	Corydalis pallida	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22500	Stephania dielsiana	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6328	Corydalis incisa	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20526	Menispermum dauricum	Species	Menispermaceae	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 NPC275625 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	15527
0.1-0.2	33404
0.2-0.3	902
0.3-0.4	22
0.4-0.5	2
0.5-0.6	0
0.6-0.7	1
0.7-0.8	1
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
0.7246	Intermediate Similarity	NPC298339
0.6667	Remote Similarity	NPC244191

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC275625 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	2862
0.1-0.2	6039
0.2-0.3	228
0.3-0.4	20
0.4-0.5	0
0.5-0.6	0
0.6-0.7	0
0.7-0.8	1
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
0.7246	Intermediate Similarity	NPD3534	Phase 3

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