NPASS Compound

Natural Product: NPC479860

Natural Product ID	NPC479860
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	DCGOUZFSTUCBET-GUGJDKNPSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	46933840
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000279] Alkaloids and derivatives [CHEMONTID:0001775] Amaryllidaceae alkaloids [CHEMONTID:0004120] Lycorine-type amaryllidaceae alkaloids

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 50 55 0 0 0 0 0 0 0 0999 V2000 5.6430 2.7229 0.3036 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7084 1.7618 1.3167 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7022 0.7942 1.4091 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6496 0.7664 0.5260 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6084 1.7250 -0.4638 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5947 2.6939 -0.5747 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6320 -0.2495 0.6556 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7048 -1.1097 1.5708 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5386 -0.3674 -0.1699 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5369 -1.3071 -0.1029 C 0 0 2 0 0 0 0 0 0 0 0 0 0.6334 -2.3773 -1.2106 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.1822 -3.5214 -0.6499 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4520 -3.2068 -0.4065 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6039 -3.9352 0.1200 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7226 -2.9333 0.1084 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1606 -1.6681 -0.2210 N 0 0 0 0 0 0 0 0 0 0 0 0 -3.3845 -0.6166 0.7152 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6802 0.6119 0.1903 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3067 1.8101 0.0613 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6007 2.8862 -0.4323 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2818 2.7010 -0.7765 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6136 1.4907 -0.6568 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3282 0.4306 -0.1644 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8493 -0.9210 0.0451 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.8487 -1.8131 -0.7317 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.7615 3.9083 -1.2495 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7461 4.8912 -0.9868 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9400 4.1957 -0.6760 O 0 0 0 0 0 0 0 0 0 0 0 0 1.9167 -2.8468 -1.3357 O 0 0 0 0 0 0 0 0 0 0 0 0 6.4406 3.4611 0.2590 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5195 1.7490 2.0313 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7895 0.0721 2.2034 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7850 1.7189 -1.1708 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5201 3.4178 -1.3597 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8551 -1.9430 0.7992 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1456 -2.0870 -2.1331 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2295 -4.5044 -0.4643 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4135 -4.3310 1.1473 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8564 -4.8193 -0.5365 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1671 -2.8639 1.1286 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4873 -3.2778 -0.6350 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4953 -0.4030 0.6854 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0734 -0.8813 1.7293 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3588 1.8995 0.3512 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4209 1.3951 -0.9462 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1643 -1.1745 1.1165 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7966 -1.6047 -1.8200 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4693 5.5710 -0.1612 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9710 5.4687 -1.9263 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1414 -3.3800 -0.5354 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 4 7 1 0 7 8 2 0 7 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 1 0 21 26 1 0 26 27 1 0 27 28 1 0 11 29 1 0 6 1 1 0 24 10 1 0 25 13 1 0 25 16 1 0 23 18 1 0 28 20 1 0 1 30 1 0 2 31 1 0 3 32 1 0 5 33 1 0 6 34 1 0 10 35 1 1 11 36 1 6 12 37 1 0 14 38 1 0 14 39 1 0 15 40 1 0 15 41 1 0 17 42 1 0 17 43 1 0 19 44 1 0 22 45 1 0 24 46 1 1 25 47 1 6 27 48 1 0 27 49 1 0 29 50 1 0 M END

Standard InCHIKey	DCGOUZFSTUCBET-GUGJDKNPSA-N
Standard InCHI	InChI=1S/C23H21NO5/c25-17-8-14-6-7-24-11-15-9-18-19(28-12-27-18)10-16(15)20(21(14)24)22(17)29-23(26)13-4-2-1-3-5-13/h1-5,8-10,17,20-22,25H,6-7,11-12H2/t17-,20-,21+,22+/m0/s1
SMILES	c1ccc(cc1)C(=O)O[C@@H]1[C@H](C=C2CCN3Cc4cc5c(cc4[C@H]1[C@@H]23)OCO5)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	391.14	Volume:	388.882 ? Van der Waals volume.
Dense:	1.006	LogP:	1.704 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.065 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.26 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	30.0
TPSA:	68.23 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	1.0	Rings:	6.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.627	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.971	Fsp³:	0.348
MCE-18:	105.484 ? 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:	0.905	Fluc inhibitor:	0.354 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.253 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.462 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.002	Promiscuous compounds:	0.097

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.291	MDCK Permeability:	-4.87
Pgp-inhibitor:	0.024	Pgp-substrate:	0.838
PAMPA:	0.473 ? 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):	0.0
20% Bioavailability (F20%):	0.065	30% Bioavailability (F30%):	0.14
50% Bioavailability (F50%):	0.796

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.978	MRP1:	0.974
Plasma Protein Binding (PPB):	79.725%	Volume Distribution (VD):	0.08
Fu:	17.258% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.931
OATP1B3 inhibitor:	0.878	BCRP inhibitor:	0.002
BSEP inhibitor:	0.948

ADMET: Metabolism

CYP1A2-inhibitor:	0.002	CYP1A2-substrate:	0.009
CYP2C19-inhibitor:	0.986	CYP2C19-substrate:	0.003
CYP2C9-inhibitor:	0.002	CYP2C9-substrate:	1.0
CYP2D6-inhibitor:	0.001	CYP2D6-substrate:	0.705
CYP3A4-inhibitor:	0.994	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.631
HLM stability:	0.77 ? 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):

9.056

Half-life (T1/2):

1.397

ADMET: Toxicity

hERG Blockers:	0.238	hERG Blockers (10um):	0.696
Human Hepatotoxicity (H-HT):	0.436	Drug-induced Liver Injury (DILI):	0.571
AMES Toxicity:	0.572	Rat Oral Acute Toxicity:	0.432
Maximum Recommended Daily Dose:	0.469	Skin Sensitization:	0.744
Carcinogencity:	0.831	Eye Corrosion:	0.001
Eye Irritation:	0.271	Respiratory Toxicity:	0.497
Drug-induced Neurotoxicity:	0.777	Ototoxicity:	0.352
Hematotoxicity:	0.219	Drug-induced Nephrotoxicity:	0.651
Genotoxicity:	0.95	RPMI-8226 Immunitoxicity:	0.061
A549 Cytotoxicity:	0.413	Hek293 Cytotoxicity:	0.417
BCF:	1.0 ? 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:	3.665 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.072 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.489 ? 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
NPO40778	Alkaloid lycorine	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[22019045]

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
Ki	1
GI50	8

Activity Type	# Activity
Individual protein	1
Cell line	6
Non-molecular	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT204	Individual protein	Acetylcholinesterase	Homo sapiens	Ki	=	540.0	nM	PMID[20655219]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT83	Cell line	MCF7	Homo sapiens	GI50	=	5000.0	nM	PMID[22019045]
NPT169	Cell line	B16-F10	Mus musculus	GI50	=	8000.0	nM	PMID[22019045]
NPT1125	Cell line	T98G	Homo sapiens	GI50	=	32000.0	nM	PMID[22019045]
NPT81	Cell line	A549	Homo sapiens	GI50	=	32000.0	nM	PMID[22019045]
NPT170	Cell line	SK-MEL-28	Homo sapiens	GI50	=	4000.0	nM	PMID[22019045]
NPT306	Cell line	PC-3	Homo sapiens	GI50	=	5000.0	nM	PMID[22019045]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	GI50	=	4000.0	nM	PMID[22019045]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	GI50	=	600.0	nM	PMID[22019045]

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 NPC479860 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	12323
0.1-0.2	34643
0.2-0.3	2802
0.3-0.4	50
0.4-0.5	12
0.5-0.6	16
0.6-0.7	3
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
0.7571	Intermediate Similarity	NPC237044
0.7534	Intermediate Similarity	NPC479867
0.7465	Intermediate Similarity	NPC474325
0.7397	Intermediate Similarity	NPC479859
0.726	Intermediate Similarity	NPC475981
0.726	Intermediate Similarity	NPC474745
0.7237	Intermediate Similarity	NPC479861
0.7105	Intermediate Similarity	NPC230098
0.7105	Intermediate Similarity	NPC479864
0.6667	Remote Similarity	NPC479865
0.6543	Remote Similarity	NPC479866
0.6351	Remote Similarity	NPC33256
0.589	Remote Similarity	NPC190332
0.589	Remote Similarity	NPC181653
0.5789	Remote Similarity	NPC474324
0.575	Remote Similarity	NPC80472
0.5714	Remote Similarity	NPC475845
0.5714	Remote Similarity	NPC607721
0.5658	Remote Similarity	NPC479856
0.56	Remote Similarity	NPC320104
0.557	Remote Similarity	NPC474708
0.5513	Remote Similarity	NPC479870
0.5455	Remote Similarity	NPC607145
0.5432	Remote Similarity	NPC479869
0.5422	Remote Similarity	NPC479857
0.5366	Remote Similarity	NPC479858
0.5301	Remote Similarity	NPC479863
0.5056	Remote Similarity	NPC479862

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC479860 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	2849
0.1-0.2	6035
0.2-0.3	264
0.3-0.4	2
0.4-0.5	0
0.5-0.6	0
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
		NPD

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