NPASS Compound

Structure

NPC299806 OpenBabel07101719512D 67 69 0 0 1 0 0 0 0 0999 V2000 4.1958 -1.1275 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4603 -5.0608 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2699 -4.9819 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2643 8.1787 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1731 9.1450 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3794 5.7087 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3172 7.0768 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2614 0.5257 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4275 7.5865 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7087 -1.3304 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1123 -4.4430 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7631 2.0632 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7470 3.8850 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1381 -0.7926 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9367 5.3909 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7422 4.4100 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0150 0.8850 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1489 2.3850 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8810 1.3850 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0150 2.8850 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0640 5.8790 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3365 -3.5229 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2913 7.4170 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2829 0.8850 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3886 2.6383 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3821 -4.5219 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2666 8.2469 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4534 6.0862 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3192 0.1908 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 3.0712 6.6521 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.9344 -0.3562 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.1489 1.3850 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8810 2.3850 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1789 -2.9840 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.1484 6.5189 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.7492 4.2919 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.4169 1.3850 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 5.0969 1.6818 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 5.4113 3.6381 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5580 0.8394 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 1.9303 -0.4472 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 3.9484 6.1719 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6635 5.4729 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.0970 6.8777 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1334 -1.9850 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9137 -0.2661 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6815 5.9610 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9079 3.3046 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8036 0.5951 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0668 -3.4441 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 1.0981 6.8322 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 3.8118 0.1737 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 1.9758 -1.4461 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.7943 2.3110 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.3300 5.1998 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 6.0048 1.2626 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 6.4049 3.7516 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5435 6.9755 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1880 7.8736 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2455 -1.5250 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.2271 -1.2157 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3472 6.7071 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9076 3.3273 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5026 -0.1200 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.7470 2.8850 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.1635 4.6069 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 14 1 0 0 0 0 2 26 1 0 0 0 0 3 26 1 0 0 0 0 4 27 1 0 0 0 0 5 27 1 0 0 0 0 6 28 1 0 0 0 0 7 28 1 0 0 0 0 11 50 1 0 0 0 0 12 54 1 0 0 0 0 13 65 1 0 0 0 0 14 29 1 0 0 0 0 15 16 1 0 0 0 0 15 21 1 0 0 0 0 17 19 1 0 0 0 0 17 32 2 0 0 0 0 18 20 2 0 0 0 0 18 32 1 0 0 0 0 19 33 2 0 0 0 0 20 33 1 0 0 0 0 21 55 1 0 0 0 0 22 26 1 0 0 0 0 23 27 1 0 0 0 0 24 32 1 0 0 0 0 25 38 1 0 0 0 0 25 39 1 0 0 0 0 29 8 1 1 0 0 0 30 9 1 1 0 0 0 30 42 1 0 0 0 0 30 44 1 0 0 0 0 31 10 1 1 0 0 0 31 41 1 0 0 0 0 31 66 1 0 0 0 0 33 65 1 0 0 0 0 34 22 1 6 0 0 0 34 45 1 0 0 0 0 34 50 1 0 0 0 0 35 23 1 6 0 0 0 35 47 1 0 0 0 0 35 51 1 0 0 0 0 36 16 1 6 0 0 0 36 48 1 0 0 0 0 36 55 1 0 0 0 0 37 24 1 6 0 0 0 37 49 1 0 0 0 0 37 54 1 0 0 0 0 38 40 1 0 0 0 0 38 56 1 6 0 0 0 39 57 2 0 0 0 0 39 67 1 0 0 0 0 40 29 1 1 0 0 0 40 52 1 0 0 0 0 41 46 1 0 0 0 0 41 53 1 1 0 0 0 42 43 1 0 0 0 0 42 58 2 0 0 0 0 43 28 1 6 0 0 0 43 67 1 0 0 0 0 44 51 2 3 0 0 0 44 59 1 0 0 0 0 45 53 2 3 0 0 0 45 60 1 0 0 0 0 46 52 2 3 0 0 0 46 61 1 0 0 0 0 47 55 1 0 0 0 0 47 62 2 0 0 0 0 48 54 1 0 0 0 0 48 63 2 0 0 0 0 49 64 2 0 0 0 0 49 66 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	942.57
Volume:	972.853
LogP:	4.226
LogD:	3.781
LogS:	-3.599
# Rotatable Bonds:	14
TPSA:	239.08
# H-Bond Aceptor:	18
# H-Bond Donor:	5
# Rings:	3
# Heavy Atoms:	18

MedChem Properties

QED Drug-Likeness Score:	0.142
Synthetic Accessibility Score:	6.08
Fsp3:	0.714
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:	-5.332
MDCK Permeability:	3.144743823213503e-05
Pgp-inhibitor:	0.999
Pgp-substrate:	0.998
Human Intestinal Absorption (HIA):	0.486
20% Bioavailability (F20%):	0.004
30% Bioavailability (F30%):	0.935

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.023
Plasma Protein Binding (PPB):	77.69652557373047%
Volume Distribution (VD):	0.495
Pgp-substrate:	14.695798873901367%

ADMET: Metabolism

CYP1A2-inhibitor:	0.002
CYP1A2-substrate:	0.019
CYP2C19-inhibitor:	0.122
CYP2C19-substrate:	0.099
CYP2C9-inhibitor:	0.136
CYP2C9-substrate:	0.019
CYP2D6-inhibitor:	0.004
CYP2D6-substrate:	0.082
CYP3A4-inhibitor:	0.887
CYP3A4-substrate:	0.276

ADMET: Excretion

Clearance (CL):	8.621
Half-life (T1/2):	0.086

ADMET: Toxicity

hERG Blockers:	0.049
Human Hepatotoxicity (H-HT):	0.988
Drug-inuced Liver Injury (DILI):	0.927
AMES Toxicity:	0.006
Rat Oral Acute Toxicity:	0.171
Maximum Recommended Daily Dose:	0.933
Skin Sensitization:	0.063
Carcinogencity:	0.059
Eye Corrosion:	0.003
Eye Irritation:	0.003
Respiratory Toxicity:	0.586

Download Data

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

Natural Product: NPC299806

Natural Product ID:	NPC299806
*Common Name:**	Didemnin A
IUPAC Name:	(2R)-N-[(3S,6S,8S,12S,13R,16S,17R,20S,23S)-13-[(2S)-butan-2-yl]-12-hydroxy-20-[(4-methoxyphenyl)methyl]-6,17,21-trimethyl-3-(2-methylpropyl)-2,5,7,10,15,19,22-heptaoxo-8-propan-2-yl-9,18-dioxa-1,4,14,21-tetrazabicyclo[21.3.0]hexacosan-16-yl]-4-methyl-2-(methylamino)pentanamide
Synonyms:	Didemnin A
Standard InCHIKey:	XQZOGOCTPKFYKC-VSZULPIASA-N
Standard InCHI:	InChI=1S/C49H78N6O12/c1-14-29(8)40-38(56)25-39(57)67-43(28(6)7)42(58)30(9)44(59)51-35(23-27(4)5)47(62)55-21-15-16-36(55)48(63)54(12)37(24-32-17-19-33(65-13)20-18-32)49(64)66-31(10)41(46(61)52-40)53-45(60)34(50-11)22-26(2)3/h17-20,26-31,34-38,40-41,43,50,56H,14-16,21-25H2,1-13H3,(H,51,59)(H,52,61)(H,53,60)/t29-,30-,31+,34+,35-,36-,37-,38-,40+,41-,43-/m0/s1
SMILES:	CC[C@H](C)[C@@H]1[C@H](CC(=O)O[C@@H](C(C)C)C(=O)[C@H](C)C(=N[C@@H](CC(C)C)C(=O)N2CCC[C@H]2C(=O)N(C)[C@@H](Cc2ccc(cc2)OC)C(=O)O[C@H](C)[C@@H](C(=N1)O)N=C([C@@H](CC(C)C)NC)O)O)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL499943
PubChem CID:	123844
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0001813] Peptidomimetics [CHEMONTID:0001961] Depsipeptides [CHEMONTID:0001994] Cyclic depsipeptides

*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
NPO28186	Trididemnum solidum	Species	Didemnidae	Eukaryota	n.a.	n.a.	n.a.	PMID[21341712]
NPO28186	Trididemnum solidum	Species	Didemnidae	Eukaryota	n.a.	n.a.	n.a.	PMID[21770369]
NPO28186	Trididemnum solidum	Species	Didemnidae	Eukaryota	n.a.	n.a.	n.a.	PMID[3373220]
NPO28186	Trididemnum solidum	Species	Didemnidae	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
IC50	2
Others	2

Activity Type	# Activity
Cell Line	4

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT137	Cell Line	L1210	Mus musculus	ID50	=	0.002	ug ml-1	PMID[532916]
NPT168	Cell Line	P388	Mus musculus	Activity	=	100.0	%	PMID[532916]
NPT137	Cell Line	L1210	Mus musculus	IC50	=	0.014	ug.mL-1	PMID[532917]
NPT393	Cell Line	HCT-116	Homo sapiens	IC50	=	32.0	nM	PMID[532918]

☑ 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 NPC299806 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	198
0.1-0.2	1048
0.2-0.3	4292
0.3-0.4	12094
0.4-0.5	9768
0.5-0.6	13827
0.6-0.7	1106
0.7-0.8	327
0.8-0.85	28
0.85-0.9	4
0.9-0.95	3
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
0.9695	High Similarity	NPC475421
0.9521	High Similarity	NPC167763
0.9521	High Similarity	NPC470903
0.9521	High Similarity	NPC470112
0.8869	High Similarity	NPC196091
0.8743	High Similarity	NPC472923
0.8421	Intermediate Similarity	NPC473502
0.8324	Intermediate Similarity	NPC473693
0.8324	Intermediate Similarity	NPC471568
0.8218	Intermediate Similarity	NPC475204
0.8218	Intermediate Similarity	NPC475123
0.8218	Intermediate Similarity	NPC46009
0.8198	Intermediate Similarity	NPC63931
0.8161	Intermediate Similarity	NPC186617
0.8125	Intermediate Similarity	NPC137627
0.8098	Intermediate Similarity	NPC248822
0.8084	Intermediate Similarity	NPC324081
0.8079	Intermediate Similarity	NPC26108
0.8033	Intermediate Similarity	NPC4910
0.8023	Intermediate Similarity	NPC306804
0.8022	Intermediate Similarity	NPC315542
0.7978	Intermediate Similarity	NPC471165
0.7965	Intermediate Similarity	NPC319320
0.7965	Intermediate Similarity	NPC287757
0.7956	Intermediate Similarity	NPC473404
0.7947	Intermediate Similarity	NPC477551
0.7943	Intermediate Similarity	NPC254700
0.7937	Intermediate Similarity	NPC477550
0.7937	Intermediate Similarity	NPC477552
0.7914	Intermediate Similarity	NPC328763
0.7898	Intermediate Similarity	NPC294516
0.7898	Intermediate Similarity	NPC107938
0.7877	Intermediate Similarity	NPC155506
0.7877	Intermediate Similarity	NPC159767
0.7872	Intermediate Similarity	NPC59827
0.7872	Intermediate Similarity	NPC184933
0.7853	Intermediate Similarity	NPC473450
0.7849	Intermediate Similarity	NPC61332
0.7849	Intermediate Similarity	NPC240130
0.7845	Intermediate Similarity	NPC269750
0.7845	Intermediate Similarity	NPC194671
0.7838	Intermediate Similarity	NPC329731
0.7833	Intermediate Similarity	NPC50016
0.7821	Intermediate Similarity	NPC273755
0.7809	Intermediate Similarity	NPC40234
0.7807	Intermediate Similarity	NPC473378
0.7807	Intermediate Similarity	NPC473407
0.7798	Intermediate Similarity	NPC145113
0.7797	Intermediate Similarity	NPC209463
0.7791	Intermediate Similarity	NPC473580
0.7778	Intermediate Similarity	NPC476227
0.7778	Intermediate Similarity	NPC262166
0.7778	Intermediate Similarity	NPC279871
0.7749	Intermediate Similarity	NPC323662
0.7749	Intermediate Similarity	NPC477527
0.7727	Intermediate Similarity	NPC326333
0.7722	Intermediate Similarity	NPC248670
0.7719	Intermediate Similarity	NPC162104
0.7714	Intermediate Similarity	NPC469243
0.7714	Intermediate Similarity	NPC475544
0.7713	Intermediate Similarity	NPC477526
0.7701	Intermediate Similarity	NPC297145
0.7701	Intermediate Similarity	NPC197743
0.7692	Intermediate Similarity	NPC329761
0.7692	Intermediate Similarity	NPC225648
0.7688	Intermediate Similarity	NPC244509
0.768	Intermediate Similarity	NPC473402
0.768	Intermediate Similarity	NPC473354
0.768	Intermediate Similarity	NPC158277
0.7667	Intermediate Similarity	NPC230611
0.7667	Intermediate Similarity	NPC89831
0.7667	Intermediate Similarity	NPC328494
0.765	Intermediate Similarity	NPC326027
0.765	Intermediate Similarity	NPC45037
0.7647	Intermediate Similarity	NPC471820
0.7647	Intermediate Similarity	NPC471821
0.764	Intermediate Similarity	NPC290755
0.764	Intermediate Similarity	NPC304074
0.764	Intermediate Similarity	NPC471771
0.764	Intermediate Similarity	NPC61004
0.7633	Intermediate Similarity	NPC81026
0.7632	Intermediate Similarity	NPC302715
0.7616	Intermediate Similarity	NPC233702
0.7614	Intermediate Similarity	NPC219350
0.7614	Intermediate Similarity	NPC194699
0.7606	Intermediate Similarity	NPC102959
0.7605	Intermediate Similarity	NPC269398
0.7605	Intermediate Similarity	NPC263493
0.7584	Intermediate Similarity	NPC223207
0.7581	Intermediate Similarity	NPC294951
0.7574	Intermediate Similarity	NPC266741
0.7574	Intermediate Similarity	NPC5620
0.7568	Intermediate Similarity	NPC477637
0.7566	Intermediate Similarity	NPC174122
0.7566	Intermediate Similarity	NPC60516
0.7566	Intermediate Similarity	NPC64140
0.756	Intermediate Similarity	NPC91953
0.7558	Intermediate Similarity	NPC473491
0.7557	Intermediate Similarity	NPC244336
0.7556	Intermediate Similarity	NPC129486
0.7553	Intermediate Similarity	NPC94862
0.7529	Intermediate Similarity	NPC39431
0.7515	Intermediate Similarity	NPC204546
0.7514	Intermediate Similarity	NPC198254
0.7514	Intermediate Similarity	NPC276506
0.7514	Intermediate Similarity	NPC274198
0.7513	Intermediate Similarity	NPC234069
0.75	Intermediate Similarity	NPC212699
0.75	Intermediate Similarity	NPC328649
0.75	Intermediate Similarity	NPC276120
0.75	Intermediate Similarity	NPC207675
0.75	Intermediate Similarity	NPC197921
0.75	Intermediate Similarity	NPC2501
0.7487	Intermediate Similarity	NPC471049
0.7487	Intermediate Similarity	NPC471050
0.7487	Intermediate Similarity	NPC471048
0.7487	Intermediate Similarity	NPC242728
0.7486	Intermediate Similarity	NPC164608
0.7485	Intermediate Similarity	NPC16188
0.7473	Intermediate Similarity	NPC476321
0.7471	Intermediate Similarity	NPC473341
0.7471	Intermediate Similarity	NPC56685
0.7463	Intermediate Similarity	NPC277306
0.7463	Intermediate Similarity	NPC469442
0.7459	Intermediate Similarity	NPC280022
0.7457	Intermediate Similarity	NPC475168
0.7457	Intermediate Similarity	NPC7817
0.7456	Intermediate Similarity	NPC469360
0.7447	Intermediate Similarity	NPC138083
0.7446	Intermediate Similarity	NPC196243
0.7444	Intermediate Similarity	NPC469479
0.744	Intermediate Similarity	NPC46098
0.744	Intermediate Similarity	NPC268841
0.744	Intermediate Similarity	NPC307357
0.7436	Intermediate Similarity	NPC123859
0.7433	Intermediate Similarity	NPC471526
0.7432	Intermediate Similarity	NPC475532
0.7412	Intermediate Similarity	NPC52748
0.7409	Intermediate Similarity	NPC477638
0.7409	Intermediate Similarity	NPC477632
0.7403	Intermediate Similarity	NPC302597
0.7401	Intermediate Similarity	NPC326349
0.7401	Intermediate Similarity	NPC323336
0.7399	Intermediate Similarity	NPC132771
0.7399	Intermediate Similarity	NPC129666
0.7391	Intermediate Similarity	NPC17698
0.7391	Intermediate Similarity	NPC165285
0.7389	Intermediate Similarity	NPC25539
0.7384	Intermediate Similarity	NPC135121
0.7382	Intermediate Similarity	NPC163961
0.7382	Intermediate Similarity	NPC283207
0.7382	Intermediate Similarity	NPC473305
0.7381	Intermediate Similarity	NPC98424
0.7381	Intermediate Similarity	NPC178662
0.7381	Intermediate Similarity	NPC476133
0.7381	Intermediate Similarity	NPC92784
0.7381	Intermediate Similarity	NPC470884
0.7374	Intermediate Similarity	NPC241794
0.7371	Intermediate Similarity	NPC261934
0.7371	Intermediate Similarity	NPC149962
0.7371	Intermediate Similarity	NPC122590
0.7371	Intermediate Similarity	NPC202198
0.7371	Intermediate Similarity	NPC5194
0.7368	Intermediate Similarity	NPC201244
0.7368	Intermediate Similarity	NPC477217
0.7368	Intermediate Similarity	NPC209509
0.7363	Intermediate Similarity	NPC469505
0.7358	Intermediate Similarity	NPC314083
0.7353	Intermediate Similarity	NPC161069
0.7349	Intermediate Similarity	NPC470392
0.7333	Intermediate Similarity	NPC144314
0.733	Intermediate Similarity	NPC470902
0.7326	Intermediate Similarity	NPC32064
0.7326	Intermediate Similarity	NPC314358
0.7321	Intermediate Similarity	NPC471264
0.7321	Intermediate Similarity	NPC471265
0.731	Intermediate Similarity	NPC476978
0.7306	Intermediate Similarity	NPC477631
0.7303	Intermediate Similarity	NPC56635
0.73	Intermediate Similarity	NPC246303
0.7297	Intermediate Similarity	NPC136797
0.7296	Intermediate Similarity	NPC50548
0.7288	Intermediate Similarity	NPC476268
0.7282	Intermediate Similarity	NPC477639
0.7273	Intermediate Similarity	NPC119652
0.7273	Intermediate Similarity	NPC97526
0.7267	Intermediate Similarity	NPC316008
0.7267	Intermediate Similarity	NPC313867
0.7251	Intermediate Similarity	NPC139326
0.7251	Intermediate Similarity	NPC251439
0.7235	Intermediate Similarity	NPC239762
0.7235	Intermediate Similarity	NPC163392
0.7228	Intermediate Similarity	NPC478005
0.7222	Intermediate Similarity	NPC469443
0.7219	Intermediate Similarity	NPC68865
0.7209	Intermediate Similarity	NPC314388
0.7209	Intermediate Similarity	NPC315283
0.7202	Intermediate Similarity	NPC248283
0.7202	Intermediate Similarity	NPC477636
0.7198	Intermediate Similarity	NPC158900

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 NPC299806 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	133
0.1-0.2	398
0.2-0.3	872
0.3-0.4	2105
0.4-0.5	2727
0.5-0.6	2257
0.6-0.7	619
0.7-0.8	39
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
0.7907	Intermediate Similarity	NPD7118	Clinical (unspecified phase)
0.7853	Intermediate Similarity	NPD7484	Phase 3
0.7853	Intermediate Similarity	NPD7485	Phase 3
0.7784	Intermediate Similarity	NPD8031	Discontinued
0.7709	Intermediate Similarity	NPD7608	Discontinued
0.7674	Intermediate Similarity	NPD7131	Phase 3
0.764	Intermediate Similarity	NPD8303	Discontinued
0.7614	Intermediate Similarity	NPD7972	Discontinued
0.7456	Intermediate Similarity	NPD7978	Discontinued
0.7447	Intermediate Similarity	NPD6851	Approved
0.7447	Intermediate Similarity	NPD6853	Approved
0.7368	Intermediate Similarity	NPD2976	Clinical (unspecified phase)
0.7356	Intermediate Similarity	NPD5348	Clinical (unspecified phase)
0.7349	Intermediate Similarity	NPD5745	Approved
0.7321	Intermediate Similarity	NPD8172	Phase 2
0.7321	Intermediate Similarity	NPD8173	Phase 2
0.7314	Intermediate Similarity	NPD7613	Discontinued
0.7314	Intermediate Similarity	NPD6390	Discontinued
0.731	Intermediate Similarity	NPD6681	Discovery
0.7294	Intermediate Similarity	NPD2239	Approved
0.7294	Intermediate Similarity	NPD2240	Approved
0.7273	Intermediate Similarity	NPD5484	Approved
0.7273	Intermediate Similarity	NPD5485	Approved
0.7263	Intermediate Similarity	NPD5356	Approved
0.7263	Intermediate Similarity	NPD5355	Approved
0.7234	Intermediate Similarity	NPD6297	Approved
0.7229	Intermediate Similarity	NPD5746	Approved
0.7229	Intermediate Similarity	NPD3136	Phase 2
0.7172	Intermediate Similarity	NPD7811	Phase 3
0.7172	Intermediate Similarity	NPD7810	Phase 3
0.7165	Intermediate Similarity	NPD6504	Approved
0.7165	Intermediate Similarity	NPD6505	Approved
0.716	Intermediate Similarity	NPD7113	Clinical (unspecified phase)
0.7159	Intermediate Similarity	NPD3536	Discontinued
0.7111	Intermediate Similarity	NPD2541	Clinical (unspecified phase)
0.711	Intermediate Similarity	NPD7596	Clinical (unspecified phase)
0.7108	Intermediate Similarity	NPD4175	Approved
0.7108	Intermediate Similarity	NPD4177	Approved
0.7097	Intermediate Similarity	NPD5137	Approved
0.7085	Intermediate Similarity	NPD7565	Approved
0.7069	Intermediate Similarity	NPD6860	Clinical (unspecified phase)
0.7043	Intermediate Similarity	NPD4652	Approved
0.7031	Intermediate Similarity	NPD7281	Phase 3
0.7031	Intermediate Similarity	NPD7280	Phase 3
0.7018	Intermediate Similarity	NPD6073	Approved
0.7018	Intermediate Similarity	NPD5725	Approved
0.7017	Intermediate Similarity	NPD6677	Suspended
0.7016	Intermediate Similarity	NPD5192	Clinical (unspecified phase)
0.7015	Intermediate Similarity	NPD6238	Discontinued
0.701	Intermediate Similarity	NPD6089	Clinical (unspecified phase)
0.6995	Remote Similarity	NPD2097	Approved
0.6983	Remote Similarity	NPD7523	Phase 3
0.6983	Remote Similarity	NPD1670	Discontinued
0.698	Remote Similarity	NPD6863	Phase 2
0.6979	Remote Similarity	NPD7132	Clinical (unspecified phase)
0.6978	Remote Similarity	NPD4227	Discontinued
0.6978	Remote Similarity	NPD8019	Approved
0.6978	Remote Similarity	NPD7495	Discontinued
0.6947	Remote Similarity	NPD42	Phase 2
0.6947	Remote Similarity	NPD6042	Phase 2
0.6941	Remote Similarity	NPD1423	Approved
0.6941	Remote Similarity	NPD5747	Discontinued
0.6941	Remote Similarity	NPD2245	Discovery
0.694	Remote Similarity	NPD5773	Approved
0.694	Remote Similarity	NPD5772	Approved
0.6928	Remote Similarity	NPD196	Phase 1
0.6927	Remote Similarity	NPD4186	Clinical (unspecified phase)
0.6919	Remote Similarity	NPD2098	Approved
0.6911	Remote Similarity	NPD5557	Phase 1
0.691	Remote Similarity	NPD6682	Clinical (unspecified phase)
0.6907	Remote Similarity	NPD6556	Clinical (unspecified phase)
0.6907	Remote Similarity	NPD5946	Clinical (unspecified phase)
0.6897	Remote Similarity	NPD1725	Approved
0.6897	Remote Similarity	NPD8162	Phase 2
0.6897	Remote Similarity	NPD8163	Clinical (unspecified phase)
0.6885	Remote Similarity	NPD4018	Clinical (unspecified phase)
0.6882	Remote Similarity	NPD1329	Clinical (unspecified phase)
0.6882	Remote Similarity	NPD1330	Phase 2
0.6882	Remote Similarity	NPD3056	Clinical (unspecified phase)
0.6878	Remote Similarity	NPD3451	Clinical (unspecified phase)
0.6875	Remote Similarity	NPD7959	Clinical (unspecified phase)
0.6872	Remote Similarity	NPD3157	Approved
0.6872	Remote Similarity	NPD3158	Phase 1
0.6872	Remote Similarity	NPD3154	Approved
0.6872	Remote Similarity	NPD3153	Approved
0.6867	Remote Similarity	NPD3676	Clinical (unspecified phase)
0.6848	Remote Similarity	NPD3465	Clinical (unspecified phase)
0.6845	Remote Similarity	NPD2041	Clinical (unspecified phase)
0.6845	Remote Similarity	NPD2042	Clinical (unspecified phase)
0.6842	Remote Similarity	NPD7634	Clinical (unspecified phase)
0.6839	Remote Similarity	NPD8014	Clinical (unspecified phase)
0.6837	Remote Similarity	NPD4434	Approved
0.6833	Remote Similarity	NPD7526	Approved
0.6833	Remote Similarity	NPD52	Approved
0.6833	Remote Similarity	NPD7527	Clinical (unspecified phase)
0.6831	Remote Similarity	NPD2513	Approved
0.6821	Remote Similarity	NPD3052	Approved
0.6821	Remote Similarity	NPD3054	Approved
0.6818	Remote Similarity	NPD5525	Clinical (unspecified phase)
0.6811	Remote Similarity	NPD7080	Clinical (unspecified phase)
0.6811	Remote Similarity	NPD7318	Phase 3
0.6809	Remote Similarity	NPD2516	Approved
0.6807	Remote Similarity	NPD3072	Approved
0.6807	Remote Similarity	NPD3073	Approved
0.6807	Remote Similarity	NPD3071	Approved
0.6806	Remote Similarity	NPD3909	Discontinued
0.6802	Remote Similarity	NPD4435	Approved
0.6802	Remote Similarity	NPD8416	Discontinued
0.6802	Remote Similarity	NPD4153	Approved
0.68	Remote Similarity	NPD7450	Phase 2
0.6798	Remote Similarity	NPD6519	Phase 2
0.6796	Remote Similarity	NPD8161	Suspended
0.6793	Remote Similarity	NPD3007	Approved
0.6793	Remote Similarity	NPD2515	Approved
0.6791	Remote Similarity	NPD6315	Phase 2
0.6791	Remote Similarity	NPD5709	Phase 3
0.6782	Remote Similarity	NPD6852	Discontinued
0.6778	Remote Similarity	NPD3688	Clinical (unspecified phase)
0.6778	Remote Similarity	NPD6419	Discontinued
0.6778	Remote Similarity	NPD2874	Phase 2
0.6778	Remote Similarity	NPD3146	Approved
0.6772	Remote Similarity	NPD2517	Approved
0.6765	Remote Similarity	NPD2614	Approved
0.6758	Remote Similarity	NPD3686	Approved
0.6758	Remote Similarity	NPD3687	Approved
0.6757	Remote Similarity	NPD6668	Clinical (unspecified phase)
0.6755	Remote Similarity	NPD4666	Phase 3
0.6751	Remote Similarity	NPD3857	Clinical (unspecified phase)
0.6751	Remote Similarity	NPD3863	Clinical (unspecified phase)
0.6747	Remote Similarity	NPD4762	Approved
0.6747	Remote Similarity	NPD4761	Approved
0.6746	Remote Similarity	NPD5339	Clinical (unspecified phase)
0.6744	Remote Similarity	NPD5729	Clinical (unspecified phase)
0.674	Remote Similarity	NPD7303	Discontinued
0.6723	Remote Similarity	NPD3655	Clinical (unspecified phase)
0.6721	Remote Similarity	NPD2052	Approved
0.672	Remote Similarity	NPD5967	Approved
0.6719	Remote Similarity	NPD6620	Discovery
0.6718	Remote Similarity	NPD3936	Clinical (unspecified phase)
0.6716	Remote Similarity	NPD4413	Clinical (unspecified phase)
0.6714	Remote Similarity	NPD3878	Approved
0.6707	Remote Similarity	NPD2584	Suspended
0.6705	Remote Similarity	NPD6623	Phase 3
0.6705	Remote Similarity	NPD3175	Clinical (unspecified phase)
0.6704	Remote Similarity	NPD8323	Discontinued
0.6703	Remote Similarity	NPD7317	Phase 3
0.6702	Remote Similarity	NPD7784	Clinical (unspecified phase)
0.6702	Remote Similarity	NPD8245	Clinical (unspecified phase)
0.6686	Remote Similarity	NPD1536	Approved
0.6685	Remote Similarity	NPD2053	Approved
0.6685	Remote Similarity	NPD2460	Phase 3
0.6685	Remote Similarity	NPD2458	Approved
0.6685	Remote Similarity	NPD22	Approved
0.6685	Remote Similarity	NPD2459	Approved
0.6684	Remote Similarity	NPD7315	Approved
0.6684	Remote Similarity	NPD5313	Approved
0.6684	Remote Similarity	NPD5312	Approved
0.6682	Remote Similarity	NPD3879	Approved
0.6682	Remote Similarity	NPD7827	Phase 1
0.6667	Remote Similarity	NPD8076	Discontinued
0.6667	Remote Similarity	NPD5263	Approved
0.6667	Remote Similarity	NPD8469	Approved
0.6667	Remote Similarity	NPD4124	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD4676	Approved
0.6649	Remote Similarity	NPD7695	Clinical (unspecified phase)
0.6648	Remote Similarity	NPD3400	Discontinued
0.6648	Remote Similarity	NPD6676	Phase 2
0.6647	Remote Similarity	NPD839	Approved
0.6647	Remote Similarity	NPD4706	Clinical (unspecified phase)
0.6647	Remote Similarity	NPD840	Approved
0.6636	Remote Similarity	NPD6824	Clinical (unspecified phase)
0.6635	Remote Similarity	NPD4130	Phase 3
0.6634	Remote Similarity	NPD5457	Discontinued
0.6633	Remote Similarity	NPD4157	Discontinued
0.6633	Remote Similarity	NPD4419	Clinical (unspecified phase)
0.6632	Remote Similarity	NPD6107	Approved
0.663	Remote Similarity	NPD6088	Approved
0.6629	Remote Similarity	NPD4782	Clinical (unspecified phase)
0.6629	Remote Similarity	NPD7153	Discontinued
0.6628	Remote Similarity	NPD3165	Approved
0.6628	Remote Similarity	NPD3166	Approved
0.6628	Remote Similarity	NPD5163	Phase 2
0.6628	Remote Similarity	NPD3167	Approved
0.6628	Remote Similarity	NPD3164	Approved
0.6617	Remote Similarity	NPD7296	Approved
0.661	Remote Similarity	NPD1538	Phase 1
0.661	Remote Similarity	NPD1519	Approved
0.661	Remote Similarity	NPD1537	Approved
0.6609	Remote Similarity	NPD2203	Discontinued
0.6603	Remote Similarity	NPD6973	Clinical (unspecified phase)
0.66	Remote Similarity	NPD7861	Discontinued
0.6593	Remote Similarity	NPD3985	Discontinued
0.6592	Remote Similarity	NPD5264	Approved
0.6592	Remote Similarity	NPD5265	Approved
0.6592	Remote Similarity	NPD4236	Phase 3
0.6592	Remote Similarity	NPD4237	Approved
0.6591	Remote Similarity	NPD1520	Approved
0.6591	Remote Similarity	NPD1521	Approved
0.6588	Remote Similarity	NPD1817	Approved
0.6588	Remote Similarity	NPD1820	Approved

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