NPASS Compound

Structure

NPC469388 OpenBabel07101719512D 46 51 0 0 1 0 0 0 0 0999 V2000 -7.7942 2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 14.9908 -0.0331 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0565 -1.5633 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3316 1.0381 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7942 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9282 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0622 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1962 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4723 -0.4089 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5847 0.0517 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3301 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.3150 0.1294 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7420 -0.4866 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 9.2026 -0.3312 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8544 -0.0260 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 10.0453 0.2071 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 13.1151 -2.7408 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 12.1169 -2.6810 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6581 -1.4781 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3364 -1.5827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 14.1085 -1.2935 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 10.9777 -1.2525 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 14.0964 -0.4804 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 4.0117 -0.5643 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 1.4181 0.6314 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 10.9329 -0.2535 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.7321 1.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 13.4805 -1.8099 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 11.8653 -1.7131 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8660 -0.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.7431 -0.6691 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.3938 -0.1814 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.2813 -0.6420 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 12.6632 -0.1758 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 13.4531 0.0170 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.7978 1.1571 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 11.7756 0.2849 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 1.5000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 12.7081 -1.1748 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -0.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 2.3262 -1.6410 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1241 -0.1037 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 5 1 0 0 0 0 3 27 1 0 0 0 0 5 6 1 0 0 0 0 6 7 1 0 0 0 0 7 8 1 0 0 0 0 8 11 1 0 0 0 0 9 10 1 0 0 0 0 9 12 1 0 0 0 0 10 13 1 0 0 0 0 11 14 1 0 0 0 0 12 15 1 0 0 0 0 13 16 1 0 0 0 0 14 18 1 0 0 0 0 15 17 1 0 0 0 0 16 27 1 0 0 0 0 19 20 1 0 0 0 0 21 22 1 0 0 0 0 23 26 1 0 0 0 0 23 31 1 0 0 0 0 24 29 1 0 0 0 0 24 32 1 0 0 0 0 25 30 1 0 0 0 0 25 33 1 0 0 0 0 26 2 1 1 0 0 0 26 39 1 0 0 0 0 27 46 1 0 0 0 0 28 4 1 6 0 0 0 28 35 1 0 0 0 0 28 40 1 0 0 0 0 29 17 1 1 0 0 0 29 41 1 0 0 0 0 30 18 1 1 0 0 0 30 42 1 0 0 0 0 31 19 1 1 0 0 0 31 43 1 0 0 0 0 32 20 1 1 0 0 0 32 43 1 0 0 0 0 33 21 1 1 0 0 0 33 44 1 0 0 0 0 34 22 1 6 0 0 0 34 35 1 0 0 0 0 34 44 1 0 0 0 0 35 36 1 6 0 0 0 36 45 2 0 0 0 0 36 46 1 0 0 0 0 37 39 2 0 0 0 0 37 41 1 0 0 0 0 37 43 1 0 0 0 0 38 40 2 0 0 0 0 38 42 1 0 0 0 0 38 44 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	652.54
Volume:	707.413
LogP:	10.325
LogD:	5.327
LogS:	-7.663
# Rotatable Bonds:	19
TPSA:	81.56
# H-Bond Aceptor:	8
# H-Bond Donor:	2
# Rings:	6
# Heavy Atoms:	8

MedChem Properties

QED Drug-Likeness Score:	0.117
Synthetic Accessibility Score:	5.425
Fsp3:	0.923
Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.978
MDCK Permeability:	4.691238791565411e-05
Pgp-inhibitor:	0.58
Pgp-substrate:	0.98
Human Intestinal Absorption (HIA):	0.008
20% Bioavailability (F20%):	0.991
30% Bioavailability (F30%):	0.994

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.017
Plasma Protein Binding (PPB):	96.8995132446289%
Volume Distribution (VD):	0.804
Pgp-substrate:	3.377185344696045%

ADMET: Metabolism

CYP1A2-inhibitor:	0.014
CYP1A2-substrate:	0.077
CYP2C19-inhibitor:	0.57
CYP2C19-substrate:	0.054
CYP2C9-inhibitor:	0.363
CYP2C9-substrate:	0.306
CYP2D6-inhibitor:	0.765
CYP2D6-substrate:	0.264
CYP3A4-inhibitor:	0.964
CYP3A4-substrate:	0.888

ADMET: Excretion

Clearance (CL):	4.987
Half-life (T1/2):	0.02

ADMET: Toxicity

hERG Blockers:	0.64
Human Hepatotoxicity (H-HT):	1.0
Drug-inuced Liver Injury (DILI):	0.972
AMES Toxicity:	0.019
Rat Oral Acute Toxicity:	0.116
Maximum Recommended Daily Dose:	0.994
Skin Sensitization:	0.972
Carcinogencity:	0.02
Eye Corrosion:	0.003
Eye Irritation:	0.008
Respiratory Toxicity:	0.437

Download Data

Data Type	Select
General Info & Identifiers & Properties
Structure MOL file
Source Organisms
Biological Activities
Similar NPs/Drugs

Natural Product: NPC469388

Natural Product ID:	NPC469388
*Common Name:**	Norbatzelladine L
IUPAC Name:	n.a.
Synonyms:	Nor-Batzelladine L
Standard InCHIKey:	HGZBYTYKEVODQE-LZBHNGPDSA-N
Standard InCHI:	InChI=1S/C38H66N6O2/c1-5-6-7-8-11-14-18-30-25-33-21-22-34-35(28(4)40-38(42-30)44(33)34)36(45)46-27(3)16-13-10-9-12-15-17-29-24-32-20-19-31-23-26(2)39-37(41-29)43(31)32/h26-35H,5-25H2,1-4H3,(H,39,41)(H,40,42)/t26-,27?,28+,29+,30+,31+,32-,33-,34-,35-/m0/s1
SMILES:	CCCCCCCC[C@@H]1C[C@@H]2CC[C@@H]3N2C(=N[C@@H]([C@@H]3C(=O)OC(CCCCCCC[C@@H]2C[C@@H]3CC[C@H]4N3C(=N[C@H](C4)C)N2)C)C)N1
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1077542
PubChem CID:	44631992
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0001346] Diazines [CHEMONTID:0000075] Pyrimidines and pyrimidine derivatives [CHEMONTID:0002202] Hydropyrimidines

*Note: the InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
**Note: the Chemical Classification was calculated by NPClassifier Version 1.5. Reference: PMID:34662515.

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO8412	Monanchora arbuscula	Species	Crambeidae	Eukaryota	n.a.	Caribbean	n.a.	PMID[19743809]
NPO33489	clathria calla	Species	Microcionidae	Eukaryota	n.a.	Caribbean	n.a.	PMID[19743809]
NPO8412	Monanchora arbuscula	Species	Crambeidae	Eukaryota	n.a.	n.a.	n.a.	PMID[25924111]
NPO8412	Monanchora arbuscula	Species	Crambeidae	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	NP ID	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	3
IC50	4
Others	11

Activity Type	# Activity
Cell Line	10
Organism	7
Others	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT82	Cell Line	MDA-MB-231	Homo sapiens	GI50	=	700.0	nM	PMID[538622]
NPT81	Cell Line	A549	Homo sapiens	GI50	=	1100.0	nM	PMID[538622]
NPT139	Cell Line	HT-29	Homo sapiens	GI50	=	1200.0	nM	PMID[538622]
NPT82	Cell Line	MDA-MB-231	Homo sapiens	TGI	=	1900.0	nM	PMID[538622]
NPT81	Cell Line	A549	Homo sapiens	TGI	=	2100.0	nM	PMID[538622]
NPT139	Cell Line	HT-29	Homo sapiens	TGI	=	2200.0	nM	PMID[538622]
NPT139	Cell Line	HT-29	Homo sapiens	LC50	=	4000.0	nM	PMID[538622]
NPT81	Cell Line	A549	Homo sapiens	LC50	=	4200.0	nM	PMID[538622]
NPT82	Cell Line	MDA-MB-231	Homo sapiens	LC50	=	4800.0	nM	PMID[538622]
NPT2679	Cell Line	LLC-MK2	Macaca mulatta	IC50	=	85000.0	nM	PMID[538623]
NPT1225	Organism	Plasmodium falciparum (isolate FcB1 / Columbia)	Plasmodium falciparum FcB1/Columbia	IC50	=	400.0	nM	PMID[538622]
NPT1021	Organism	Leishmania infantum	Leishmania infantum	IC50	=	2000.0	nM	PMID[538623]
NPT1021	Organism	Leishmania infantum	Leishmania infantum	Activity	=	65.0	%	PMID[538623]
NPT1021	Organism	Leishmania infantum	Leishmania infantum	Activity	=	30.0	%	PMID[538623]
NPT1021	Organism	Leishmania infantum	Leishmania infantum	Activity	=	82.0	%	PMID[538623]
NPT2	Others	Unspecified		Ratio IC50	=	12.0	n.a.	PMID[538623]
NPT580	Organism	Trypanosoma cruzi	Trypanosoma cruzi	Ratio IC50	=	54.0	n.a.	PMID[538623]
NPT580	Organism	Trypanosoma cruzi	Trypanosoma cruzi	IC50	=	7000.0	nM	PMID[538623]

☑ Note for Activity Records:
☉ The quantitative biological activities were primarily integrated from ChEMBL (Version-30) database and were also directly collected from PubMed literature. PubMed PMID was provided as the reference link for each activity record.

Chemically structural similarity: I. Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes 4,3285 NPs with experimentally-derived bioactivity available in NPASS)

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules. Tc lies between [0, 1] where '1' indicates the highest similarity. What is Tanimoto coefficient

● The left chart: Distribution of similarity level between NPC469388 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	157
0.1-0.2	5023
0.2-0.3	19400
0.3-0.4	15222
0.4-0.5	2679
0.5-0.6	172
0.6-0.7	30
0.7-0.8	10
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	3

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC472737
1.0	High Similarity	NPC469389
0.8627	High Similarity	NPC472736
0.7724	Intermediate Similarity	NPC311244
0.7724	Intermediate Similarity	NPC324722
0.7724	Intermediate Similarity	NPC198644
0.7686	Intermediate Similarity	NPC477518
0.7007	Intermediate Similarity	NPC477519
0.6923	Remote Similarity	NPC261730
0.6739	Remote Similarity	NPC142761
0.6599	Remote Similarity	NPC327517
0.6599	Remote Similarity	NPC322372
0.6599	Remote Similarity	NPC319334
0.6515	Remote Similarity	NPC469387
0.6455	Remote Similarity	NPC304454
0.64	Remote Similarity	NPC469423
0.6376	Remote Similarity	NPC321485
0.6376	Remote Similarity	NPC317377
0.6019	Remote Similarity	NPC216090
0.5935	Remote Similarity	NPC87919
0.5905	Remote Similarity	NPC208657
0.5893	Remote Similarity	NPC277918
0.5882	Remote Similarity	NPC476449
0.584	Remote Similarity	NPC467022
0.5667	Remote Similarity	NPC476261
0.5667	Remote Similarity	NPC471635
0.5667	Remote Similarity	NPC25033
0.5667	Remote Similarity	NPC119225
0.5667	Remote Similarity	NPC470382
0.5655	Remote Similarity	NPC473955
0.563	Remote Similarity	NPC469998
0.562	Remote Similarity	NPC3604

Chemically structural similarity: II. Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC469388 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	89
0.1-0.2	773
0.2-0.3	4934
0.3-0.4	2827
0.4-0.5	447
0.5-0.6	73
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	Drug ID	Developmental Stage
0.64	Remote Similarity	NPD2696	Approved
0.64	Remote Similarity	NPD2694	Approved
0.64	Remote Similarity	NPD2695	Approved
0.64	Remote Similarity	NPD2697	Approved
0.605	Remote Similarity	NPD4825	Clinical (unspecified phase)
0.5948	Remote Similarity	NPD6699	Clinical (unspecified phase)
0.5929	Remote Similarity	NPD3176	Clinical (unspecified phase)
0.584	Remote Similarity	NPD1829	Clinical (unspecified phase)
0.584	Remote Similarity	NPD1828	Approved
0.584	Remote Similarity	NPD1827	Clinical (unspecified phase)
0.5726	Remote Similarity	NPD6122	Discontinued
0.5714	Remote Similarity	NPD8175	Discontinued
0.562	Remote Similarity	NPD5349	Clinical (unspecified phase)

Bioactivity similarity: Similar Natural Products in NPASS

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