NPASS Compound

Structure

NPC469387 OpenBabel07101719512D 51 55 0 0 1 0 0 0 0 0999 V2000 0.5381 -7.2593 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.8397 -5.0463 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4932 -8.2583 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3359 -8.7966 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2235 -8.3360 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 12.6926 -4.9932 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0662 -8.8743 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 13.5586 -4.4932 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 11.8266 -4.4932 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9538 -8.4137 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 14.4247 -4.9932 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 17.8888 -1.9932 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 10.9606 -4.9932 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 17.0227 -1.4932 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 19.4276 -5.4932 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7965 -8.9520 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 15.2907 -4.4932 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 18.8398 -4.6842 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.3507 -8.9205 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.9742 -8.1386 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 18.7548 -1.4932 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 18.8398 -6.3022 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 10.0945 -4.4932 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 16.1567 -1.9932 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5268 -9.0297 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6907 -6.0352 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6841 -8.4914 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 7.4144 -8.5691 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 16.1567 -4.9932 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 17.8888 -4.9932 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.4233 -7.3041 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.3625 -6.4932 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 17.0227 -4.4932 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 9.2285 -5.9932 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 17.0227 -3.4932 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 20.4868 -1.4932 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 17.0227 -6.4932 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6166 -7.0317 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 21.3529 -1.9932 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 20.4868 -0.4932 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 17.0227 -7.4932 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 19.6208 -1.9932 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 6.9136 -6.2748 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 5.7290 -7.4924 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 16.1567 -5.9932 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 17.8888 -5.9932 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 7.4593 -7.5701 0.0000 N 0 3 0 0 0 0 0 0 0 0 0 0 10.0945 -6.4932 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 17.8888 -2.9932 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 9.2285 -4.9932 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 16.1567 -2.9932 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 3 1 0 0 0 0 2 26 1 0 0 0 0 3 4 1 0 0 0 0 4 5 1 0 0 0 0 5 7 1 0 0 0 0 6 8 1 0 0 0 0 6 9 1 0 0 0 0 7 10 1 0 0 0 0 8 11 1 0 0 0 0 9 13 1 0 0 0 0 10 16 1 0 0 0 0 11 17 1 0 0 0 0 12 14 1 0 0 0 0 12 21 1 0 0 0 0 13 23 1 0 0 0 0 14 24 1 0 0 0 0 15 18 1 0 0 0 0 15 22 1 0 0 0 0 16 27 1 0 0 0 0 17 29 1 0 0 0 0 18 30 1 0 0 0 0 19 20 1 0 0 0 0 19 28 1 0 0 0 0 20 31 1 0 0 0 0 21 42 1 0 0 0 0 22 46 1 0 0 0 0 23 50 1 0 0 0 0 24 51 1 0 0 0 0 25 27 1 0 0 0 0 25 28 1 0 0 0 0 26 32 2 0 0 0 0 26 43 1 0 0 0 0 27 44 1 0 0 0 0 28 47 1 0 0 0 0 29 33 1 0 0 0 0 29 45 1 0 0 0 0 30 33 2 0 0 0 0 30 46 1 0 0 0 0 31 32 1 0 0 0 0 31 47 2 0 0 0 0 32 34 1 0 0 0 0 33 35 1 0 0 0 0 34 48 2 0 0 0 0 34 50 1 0 0 0 0 35 49 2 0 0 0 0 35 51 1 0 0 0 0 36 39 2 0 0 0 0 36 40 1 0 0 0 0 36 42 1 0 0 0 0 37 41 2 0 0 0 0 37 45 1 0 0 0 0 37 46 1 0 0 0 0 38 43 1 0 0 0 0 38 44 2 0 0 0 0 38 47 1 0 0 0 0 M CHG 1 47 1 M END $$$$

Physi-Chem Properties

Molecular Weight:	638.52
Volume:	690.117
LogP:	9.93
LogD:	5.253
LogS:	-7.595
# Rotatable Bonds:	18
TPSA:	81.56
# H-Bond Aceptor:	8
# H-Bond Donor:	2
# Rings:	6
# Heavy Atoms:	8

MedChem Properties

QED Drug-Likeness Score:	0.128
Synthetic Accessibility Score:	5.422
Fsp3:	0.921
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:	-4.962
MDCK Permeability:	5.239303573034704e-05
Pgp-inhibitor:	0.724
Pgp-substrate:	0.984
Human Intestinal Absorption (HIA):	0.008
20% Bioavailability (F20%):	0.984
30% Bioavailability (F30%):	0.992

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.019
Plasma Protein Binding (PPB):	96.62724304199219%
Volume Distribution (VD):	0.849
Pgp-substrate:	3.5127108097076416%

ADMET: Metabolism

CYP1A2-inhibitor:	0.014
CYP1A2-substrate:	0.074
CYP2C19-inhibitor:	0.58
CYP2C19-substrate:	0.054
CYP2C9-inhibitor:	0.419
CYP2C9-substrate:	0.281
CYP2D6-inhibitor:	0.705
CYP2D6-substrate:	0.253
CYP3A4-inhibitor:	0.962
CYP3A4-substrate:	0.894

ADMET: Excretion

Clearance (CL):	5.029
Half-life (T1/2):	0.023

ADMET: Toxicity

hERG Blockers:	0.622
Human Hepatotoxicity (H-HT):	1.0
Drug-inuced Liver Injury (DILI):	0.971
AMES Toxicity:	0.02
Rat Oral Acute Toxicity:	0.124
Maximum Recommended Daily Dose:	0.994
Skin Sensitization:	0.971
Carcinogencity:	0.022
Eye Corrosion:	0.003
Eye Irritation:	0.008
Respiratory Toxicity:	0.461

Download Data

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

Natural Product: NPC469387

Natural Product ID:	NPC469387
*Common Name:**	Dinordehydrobatzelladine B
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	STLJTXDDSWZXCQ-YFRLFCAZSA-N
Standard InCHI:	InChI=1S/C38H61N9O4.ClH/c1-3-4-5-7-10-16-27-25-28-19-20-31-32(26(2)43-38(44-27)47(28)31)34(48)50-23-13-9-6-8-11-17-29-33(30-18-15-22-46(30)37(41)45-29)35(49)51-24-14-12-21-42-36(39)40;/h27-29H,3-25H2,1-2H3,(H6,39,40,41,42,45);1H/t27-,28+,29-;/m1./s1
SMILES:	CCCCCCCC1CC2CCC3=[N+]2C(=NC(=C3C(=O)OCCCCCCCC4C(=C5CCCN5C(=N4)N)C(=O)OCCCCN=C(N)N)C)N1.[Cl-]
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1077541
PubChem CID:	46882525
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0001346] Diazines [CHEMONTID:0000075] Pyrimidines and pyrimidine derivatives [CHEMONTID:0001319] Pyrimidinecarboxylic acids and derivatives [CHEMONTID:0002415] Pyrimidinecarboxylic acids

*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
NPO33489	clathria calla	Species	Microcionidae	Eukaryota	n.a.	Caribbean	n.a.	PMID[19743809]
NPO8412	Monanchora arbuscula	Species	Crambeidae	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	2
IC50	1
Others	4

Activity Type	# Activity
Cell Line	6
Organism	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT139	Cell Line	HT-29	Homo sapiens	GI50	=	6200.0	nM	PMID[473768]
NPT81	Cell Line	A549	Homo sapiens	GI50	=	7900.0	nM	PMID[473768]
NPT81	Cell Line	A549	Homo sapiens	TGI	>	14000.0	nM	PMID[473768]
NPT139	Cell Line	HT-29	Homo sapiens	TGI	>	14000.0	nM	PMID[473768]
NPT81	Cell Line	A549	Homo sapiens	LC50	>	14000.0	nM	PMID[473768]
NPT139	Cell Line	HT-29	Homo sapiens	LC50	>	14000.0	nM	PMID[473768]
NPT1225	Organism	Plasmodium falciparum (isolate FcB1 / Columbia)	Plasmodium falciparum FcB1/Columbia	IC50	=	800.0	nM	PMID[473768]

☑ 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 NPC469387 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	135
0.1-0.2	2371
0.2-0.3	22853
0.3-0.4	15348
0.4-0.5	1860
0.5-0.6	95
0.6-0.7	20
0.7-0.8	2
0.8-0.85	11
0.85-0.9	1
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.8898	High Similarity	NPC469423
0.8583	High Similarity	NPC198644
0.8583	High Similarity	NPC311244
0.8583	High Similarity	NPC324722
0.8305	Intermediate Similarity	NPC467022
0.6885	Remote Similarity	NPC469424
0.6733	Remote Similarity	NPC477519
0.6711	Remote Similarity	NPC142761
0.664	Remote Similarity	NPC472736
0.6515	Remote Similarity	NPC469389
0.6515	Remote Similarity	NPC469388
0.6515	Remote Similarity	NPC472737
0.6414	Remote Similarity	NPC261730
0.6299	Remote Similarity	NPC476449
0.6127	Remote Similarity	NPC245534
0.5986	Remote Similarity	NPC471261
0.5976	Remote Similarity	NPC327517
0.5976	Remote Similarity	NPC319334
0.5976	Remote Similarity	NPC322372
0.5942	Remote Similarity	NPC147238
0.5879	Remote Similarity	NPC321485
0.5879	Remote Similarity	NPC317377
0.5676	Remote Similarity	NPC477518
0.5649	Remote Similarity	NPC471256
0.5639	Remote Similarity	NPC241426

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 NPC469387 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	99
0.1-0.2	406
0.2-0.3	3338
0.3-0.4	4822
0.4-0.5	465
0.5-0.6	20
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
0.5959	Remote Similarity	NPD4816	Clinical (unspecified phase)
0.5734	Remote Similarity	NPD6936	Clinical (unspecified phase)
0.5734	Remote Similarity	NPD6935	Phase 3
0.5694	Remote Similarity	NPD6918	Phase 1
0.5633	Remote Similarity	NPD6077	Discontinued

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