NPASS Compound

Natural Product: NPC514568

Natural Product ID	NPC514568
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Corydine methyl ether
IUPAC Name	(6~{a}~{S})-1,2,10,11-tetramethoxy-6-methyl-5,6,6~{a},7-tetrahydro-4~{H}-dibenzo[de,g]quinoline
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic 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 51 54 0 0 0 0 0 0 0 0999 V2000 5.4638 -1.8414 0.2353 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4452 -0.9169 -0.0011 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1359 -1.1799 0.3766 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8449 -2.3665 0.9904 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5503 -2.6357 1.3674 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5534 -1.7128 1.1352 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7832 -2.1392 1.5669 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8947 -1.3625 1.0540 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.5415 -0.0582 0.4550 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6333 0.7688 0.2039 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4198 2.0172 -0.3016 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1506 2.4574 -0.5530 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8753 3.7161 -1.0646 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9483 4.5777 -1.3368 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0375 1.6253 -0.2950 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1659 2.2104 -0.5453 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6590 3.1494 0.4961 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2583 0.3772 0.1924 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8624 -0.5047 0.5174 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1297 -0.2289 0.1252 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6085 0.8610 -0.5328 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8436 0.7126 -1.9881 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9593 0.1672 0.5068 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9870 -1.2308 -0.0690 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8769 -2.0577 0.2631 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.3404 -2.8206 -0.8124 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1488 -2.8631 -0.1290 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6555 -1.9815 1.3283 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4190 -1.5779 -0.2308 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6113 -3.1023 1.1892 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3244 -3.5997 1.8572 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9075 -3.2364 1.3068 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7244 -2.1819 2.6984 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5132 -1.0436 1.9766 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2617 2.6743 -0.5115 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5580 5.5621 -1.6713 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5907 4.1651 -2.1364 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5215 4.7454 -0.4199 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7094 2.5602 1.4149 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6577 3.4986 0.1923 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9044 3.9433 0.6245 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9234 0.4643 -2.5007 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1956 1.7095 -2.3034 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6850 0.0067 -2.1094 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1568 0.0986 1.5826 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7879 0.7240 0.0423 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1300 -1.2330 -1.1628 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9108 -1.7258 0.3501 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8676 -2.5634 -1.7752 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5968 -3.8944 -0.6361 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2638 -2.7338 -0.9628 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 1 0 12 15 1 0 15 16 1 0 16 17 1 0 15 18 2 0 18 19 1 0 19 20 2 0 20 21 1 0 21 22 1 0 10 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 20 3 1 0 19 6 1 0 25 8 1 0 18 9 1 0 1 27 1 0 1 28 1 0 1 29 1 0 4 30 1 0 5 31 1 0 7 32 1 0 7 33 1 0 8 34 1 1 11 35 1 0 14 36 1 0 14 37 1 0 14 38 1 0 17 39 1 0 17 40 1 0 17 41 1 0 22 42 1 0 22 43 1 0 22 44 1 0 23 45 1 0 23 46 1 0 24 47 1 0 24 48 1 0 26 49 1 0 26 50 1 0 26 51 1 0 M END

Standard InCHIKey	NMGKOLWJHJBERW-AWEZNQCLSA-N
Standard InCHI	InChI=1S/C21H25NO4/c1-22-9-8-13-11-16(24-3)21(26-5)19-17(13)14(22)10-12-6-7-15(23-2)20(25-4)18(12)19/h6-7,11,14H,8-10H2,1-5H3/t14-/m0/s1
SMILES	COC1=CC=C2C[C@H]3C4=C(C=C(OC)C(OC)=C4C2=C1OC)CCN3C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	355.18	Volume:	367.885 ? Van der Waals volume.
Dense:	0.965	LogP:	2.274 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.458 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.227 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	20.0
TPSA:	40.16 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	0.0	Rings:	4.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.84	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.997	Fsp³:	0.429
MCE-18:	75.133 ? 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:	0.202	Fluc inhibitor:	0.104 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.662 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.389 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.003	Promiscuous compounds:	0.923

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.627	MDCK Permeability:	-4.635
Pgp-inhibitor:	0.333	Pgp-substrate:	0.659
PAMPA:	0.026 ? 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):	0.059
20% Bioavailability (F20%):	0.41	30% Bioavailability (F30%):	0.219
50% Bioavailability (F50%):	0.938

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.377	MRP1:	0.95
Plasma Protein Binding (PPB):	64.202%	Volume Distribution (VD):	0.28
Fu:	32.49% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.831
OATP1B3 inhibitor:	0.983	BCRP inhibitor:	0.74
BSEP inhibitor:	0.927

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	0.01
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.831	CYP2C9-substrate:	0.004
CYP2D6-inhibitor:	0.985	CYP2D6-substrate:	0.039
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.365
CYP2B6-substrate:	0.999	CYP2C8-inhibitor:	0.02
HLM stability:	0.218 ? 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):

8.881

Half-life (T1/2):

2.934

ADMET: Toxicity

hERG Blockers:	0.49	hERG Blockers (10um):	0.708
Human Hepatotoxicity (H-HT):	0.514	Drug-induced Liver Injury (DILI):	0.045
AMES Toxicity:	0.605	Rat Oral Acute Toxicity:	0.718
Maximum Recommended Daily Dose:	0.891	Skin Sensitization:	0.454
Carcinogencity:	0.792	Eye Corrosion:	0.001
Eye Irritation:	0.09	Respiratory Toxicity:	0.933
Drug-induced Neurotoxicity:	0.906	Ototoxicity:	0.31
Hematotoxicity:	0.193	Drug-induced Nephrotoxicity:	0.347
Genotoxicity:	0.711	RPMI-8226 Immunitoxicity:	0.078
A549 Cytotoxicity:	0.181	Hek293 Cytotoxicity:	0.329
BCF:	2.31 ? 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:	4.148 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.671 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.835 ? 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
NPO54828	Ocotea holdrigeiana	Genus	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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 NPC514568 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	32684
0.1-0.2	15898
0.2-0.3	977
0.3-0.4	228
0.4-0.5	32
0.5-0.6	25
0.6-0.7	8
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8333	Intermediate Similarity	NPC247389
0.7193	Intermediate Similarity	NPC117188
0.7193	Intermediate Similarity	NPC145832
0.7193	Intermediate Similarity	NPC600388
0.7069	Intermediate Similarity	NPC205421
0.7069	Intermediate Similarity	NPC607722
0.6964	Remote Similarity	NPC326316
0.6964	Remote Similarity	NPC81733
0.6909	Remote Similarity	NPC99659
0.6909	Remote Similarity	NPC325871
0.6557	Remote Similarity	NPC219341
0.65	Remote Similarity	NPC474931
0.6333	Remote Similarity	NPC136508
0.6094	Remote Similarity	NPC320223
0.5909	Remote Similarity	NPC114364
0.5833	Remote Similarity	NPC158376
0.5781	Remote Similarity	NPC266753
0.5781	Remote Similarity	NPC160298
0.5714	Remote Similarity	NPC63997
0.5714	Remote Similarity	NPC16805
0.5714	Remote Similarity	NPC167546
0.5606	Remote Similarity	NPC600118
0.5556	Remote Similarity	NPC605949
0.5469	Remote Similarity	NPC306902
0.5469	Remote Similarity	NPC232924
0.5397	Remote Similarity	NPC609009
0.5373	Remote Similarity	NPC610764
0.5303	Remote Similarity	NPC476432
0.5303	Remote Similarity	NPC24264
0.5294	Remote Similarity	NPC128560
0.5294	Remote Similarity	NPC229166
0.5172	Remote Similarity	NPC213206
0.5172	Remote Similarity	NPC188163
0.5172	Remote Similarity	NPC328750
0.5161	Remote Similarity	NPC470925
0.5135	Remote Similarity	NPC606311
0.5077	Remote Similarity	NPC253043
0.5075	Remote Similarity	NPC19520
0.5067	Remote Similarity	NPC112248

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC514568 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4482
0.1-0.2	4459
0.2-0.3	194
0.3-0.4	14
0.4-0.5	0
0.5-0.6	1
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
0.5172	Remote Similarity	NPD4664	Clinical (unspecified phase)

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