NPASS Compound

Natural Product: NPC479870

Natural Product ID	NPC479870
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	HHUMLACGQZFTEU-FNAHDJPLSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	54764246
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 52 56 0 0 0 0 0 0 0 0999 V2000 -0.6235 3.2826 -1.7423 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6647 2.4836 -1.9177 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7716 2.4848 -0.9498 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0004 1.2636 -0.3337 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8874 0.8648 0.3535 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.1870 0.6013 1.8112 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1463 0.1442 2.4957 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8627 -0.2705 3.8989 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6768 -0.4342 3.8961 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9979 -0.8389 2.5701 N 0 0 0 0 0 0 0 0 0 0 0 0 2.3024 -0.5622 2.0837 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3470 -0.3030 0.6137 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5788 0.0467 0.1151 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7447 0.3111 -1.2456 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6621 0.2197 -2.0929 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4342 -0.1387 -1.5372 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2265 -0.4038 -0.2256 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0144 -0.7834 0.4417 C 0 0 1 0 0 0 0 0 0 0 0 0 0.1041 -0.0259 1.7733 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.3120 -0.4659 -0.1575 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.4754 -0.5853 -1.5031 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4283 -1.5312 -1.8788 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0882 -2.8866 -1.3980 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9026 -3.5376 -0.5879 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1061 0.5288 -3.3637 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5322 0.4203 -3.3640 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8421 0.6766 -2.0097 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2187 3.3242 -2.4212 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5671 3.9538 -0.8806 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6842 1.8354 -2.7819 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6887 2.8229 -1.5160 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5689 3.2292 -0.1415 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0582 1.5973 0.2617 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1253 0.7536 2.2824 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3498 -1.2115 4.1745 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1034 0.4956 4.6371 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8843 -1.2846 4.5904 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1674 0.4738 4.2498 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9860 -1.3991 2.3671 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6998 0.3601 2.5988 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4621 0.1294 0.7579 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6250 -0.2002 -2.2202 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0910 -1.8893 0.6746 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6142 0.9543 1.6314 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0472 -1.2202 0.2897 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4170 -1.2471 -1.4763 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4781 -1.5892 -2.9869 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1528 -3.3562 -1.7158 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7076 -4.5310 -0.2033 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8222 -3.0584 -0.2842 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8342 -0.6420 -3.5789 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9975 1.1387 -4.0539 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 1 0 4 5 1 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 1 0 12 13 2 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 1 0 18 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 2 0 15 25 1 0 25 26 1 0 26 27 1 0 20 5 1 0 19 7 1 0 19 10 1 0 17 12 1 0 27 14 1 0 1 28 1 0 1 29 1 0 2 30 1 0 3 31 1 0 3 32 1 0 5 33 1 1 6 34 1 0 8 35 1 0 8 36 1 0 9 37 1 0 9 38 1 0 11 39 1 0 11 40 1 0 13 41 1 0 16 42 1 0 18 43 1 1 19 44 1 6 20 45 1 1 22 46 1 0 22 47 1 0 23 48 1 0 24 49 1 0 24 50 1 0 26 51 1 0 26 52 1 0 M END

Standard InCHIKey	HHUMLACGQZFTEU-FNAHDJPLSA-N
Standard InCHI	InChI=1S/C22H25NO4/c1-3-7-24-19-9-14-5-6-23-12-15-10-17-18(27-13-26-17)11-16(15)20(21(14)23)22(19)25-8-4-2/h3-4,9-11,19-22H,1-2,5-8,12-13H2/t19-,20-,21+,22+/m0/s1
SMILES	C=CCO[C@H]1C=C2CCN3Cc4cc5c(cc4[C@@H]([C@@H]23)[C@@H]1OCC=C)OCO5

Calculated Properties

Physi-Chem Properties

Molecular Weight:	367.18	Volume:	376.625 ? Van der Waals volume.
Dense:	0.975	LogP:	2.415 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.495 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.012 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	25.0
TPSA:	40.16 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	0.0	Rings:	5.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.723	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.478	Fsp³:	0.455
MCE-18:	87.5 ? 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:	0.517	Fluc inhibitor:	0.111 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.154 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.123 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.003	Promiscuous compounds:	0.309

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.582	MDCK Permeability:	-4.757
Pgp-inhibitor:	0.336	Pgp-substrate:	0.037
PAMPA:	0.0 ? 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):	0.0
20% Bioavailability (F20%):	0.419	30% Bioavailability (F30%):	0.686
50% Bioavailability (F50%):	0.794

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.491	MRP1:	0.75
Plasma Protein Binding (PPB):	89.562%	Volume Distribution (VD):	0.091
Fu:	13.298% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.977
OATP1B3 inhibitor:	0.829	BCRP inhibitor:	0.344
BSEP inhibitor:	0.975

ADMET: Metabolism

CYP1A2-inhibitor:	0.77	CYP1A2-substrate:	0.933
CYP2C19-inhibitor:	0.793	CYP2C19-substrate:	0.101
CYP2C9-inhibitor:	0.401	CYP2C9-substrate:	0.999
CYP2D6-inhibitor:	0.915	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	0.028	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.031	CYP2C8-inhibitor:	0.019
HLM stability:	0.387 ? 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):

11.249

Half-life (T1/2):

1.788

ADMET: Toxicity

hERG Blockers:	0.289	hERG Blockers (10um):	0.643
Human Hepatotoxicity (H-HT):	0.466	Drug-induced Liver Injury (DILI):	0.322
AMES Toxicity:	0.614	Rat Oral Acute Toxicity:	0.715
Maximum Recommended Daily Dose:	0.655	Skin Sensitization:	0.843
Carcinogencity:	0.777	Eye Corrosion:	0.026
Eye Irritation:	0.683	Respiratory Toxicity:	0.884
Drug-induced Neurotoxicity:	0.777	Ototoxicity:	0.337
Hematotoxicity:	0.348	Drug-induced Nephrotoxicity:	0.247
Genotoxicity:	0.893	RPMI-8226 Immunitoxicity:	0.07
A549 Cytotoxicity:	0.109	Hek293 Cytotoxicity:	0.3
BCF:	1.336 ? 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:	3.494 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.229 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.626 ? 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
GI50	8

Activity Type	# Activity
Cell line	6
Non-molecular	2

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
NPT83	Cell line	MCF7	Homo sapiens	GI50	=	200.0	nM	PMID[22019045]
NPT169	Cell line	B16-F10	Mus musculus	GI50	=	4000.0	nM	PMID[22019045]
NPT1125	Cell line	T98G	Homo sapiens	GI50	=	4000.0	nM	PMID[22019045]
NPT81	Cell line	A549	Homo sapiens	GI50	=	4000.0	nM	PMID[22019045]
NPT170	Cell line	SK-MEL-28	Homo sapiens	GI50	=	6000.0	nM	PMID[22019045]
NPT306	Cell line	PC-3	Homo sapiens	GI50	=	1000.0	nM	PMID[22019045]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	GI50	=	2000.0	nM	PMID[22019045]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	GI50	=	30.0	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 NPC479870 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	27268
0.1-0.2	21961
0.2-0.3	557
0.3-0.4	36
0.4-0.5	10
0.5-0.6	16
0.6-0.7	7
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
0.7385	Intermediate Similarity	NPC474324
0.7273	Intermediate Similarity	NPC475845
0.7059	Intermediate Similarity	NPC474708
0.6857	Remote Similarity	NPC479869
0.6667	Remote Similarity	NPC479859
0.6667	Remote Similarity	NPC479863
0.6282	Remote Similarity	NPC479862
0.6056	Remote Similarity	NPC607721
0.6029	Remote Similarity	NPC190332
0.6029	Remote Similarity	NPC181653
0.589	Remote Similarity	NPC237044
0.5811	Remote Similarity	NPC474325
0.5658	Remote Similarity	NPC475981
0.5658	Remote Similarity	NPC474745
0.5658	Remote Similarity	NPC479858
0.557	Remote Similarity	NPC230098
0.557	Remote Similarity	NPC479864
0.5513	Remote Similarity	NPC479857
0.5513	Remote Similarity	NPC479860
0.5513	Remote Similarity	NPC479867
0.5493	Remote Similarity	NPC320104
0.5342	Remote Similarity	NPC479856
0.5309	Remote Similarity	NPC479861
0.5238	Remote Similarity	NPC479865
0.5119	Remote Similarity	NPC479866
0.5068	Remote Similarity	NPC246597

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC479870 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5045
0.1-0.2	4047
0.2-0.3	57
0.3-0.4	1
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