NPASS Compound

Natural Product: NPC323608

Natural Product ID	NPC323608
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	GTUJJVSZIHQLHA-XPWFQUROSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	14474988
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000289] Nucleosides, nucleotides, and analogues [CHEMONTID:0003796] (3'->5')-dinucleotides and analogues [CHEMONTID:0003394] (3'->5')-dinucleotides

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 71 76 0 0 0 0 0 0 0 0999 V2000 8.4618 -0.4797 -1.3796 C 0 0 0 0 0 0 0 0 0 0 0 0 8.9575 0.7503 -1.0957 N 0 0 0 0 0 0 0 0 0 0 0 0 8.4429 1.4622 -0.0857 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4140 0.9193 0.6441 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9248 -0.3519 0.3265 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4552 -1.0309 -0.6788 N 0 0 0 0 0 0 0 0 0 0 0 0 5.9291 -0.6744 1.1659 N 0 0 0 0 0 0 0 0 0 0 0 0 5.7839 0.3685 2.0035 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6687 1.3174 1.6920 N 0 0 0 0 0 0 0 0 0 0 0 0 5.1445 -1.8631 1.2149 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8347 -2.5006 -0.0855 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5658 -1.8004 -0.5099 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9849 -1.3914 0.8018 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9128 -1.5707 1.7839 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3627 -0.0157 0.7671 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4489 -0.0095 -0.2852 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6549 1.4660 -0.4434 P 0 0 0 0 0 0 0 0 0 0 0 0 0.7221 1.8788 -1.8957 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4037 2.6541 0.4995 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9650 1.3719 0.0061 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5278 0.2003 -0.4704 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7418 0.4352 -1.3341 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4414 -0.7385 -1.2306 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2589 -1.2953 0.0088 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1295 -0.5804 0.6805 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5029 0.3067 1.6569 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4931 -1.2873 0.7411 N 0 0 0 0 0 0 0 0 0 0 0 0 -4.6829 -1.2551 2.0884 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0006 -1.2624 2.2807 N 0 0 0 0 0 0 0 0 0 0 0 0 -6.6720 -1.2978 1.1246 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.0225 -1.3180 0.8239 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.3497 -1.3541 -0.4840 N 0 0 0 0 0 0 0 0 0 0 0 0 -7.4331 -1.3702 -1.4603 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1345 -1.3497 -1.1298 N 0 0 0 0 0 0 0 0 0 0 0 0 -5.7030 -1.3135 0.1436 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.0245 -1.3023 1.8181 N 0 0 0 0 0 0 0 0 0 0 0 0 -3.5378 1.6335 -0.8879 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6846 1.7673 -1.6631 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.6012 3.0917 -1.2054 P 0 0 0 0 0 0 0 0 0 0 0 0 -5.3385 3.4907 0.2322 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.2458 2.8098 -1.4777 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1542 4.4007 -2.1895 O 0 0 0 0 0 0 0 0 0 0 0 0 3.7841 -0.7590 -1.3850 O 0 0 0 0 0 0 0 0 0 0 0 0 4.4766 -3.8454 0.1658 O 0 0 0 0 0 0 0 0 0 0 0 0 8.9315 2.7489 0.2429 N 0 0 0 0 0 0 0 0 0 0 0 0 8.9085 -1.0311 -2.2122 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0764 0.4863 2.8276 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6029 -2.6557 1.8769 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6150 -2.5244 -0.8342 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9200 -2.5445 -1.0541 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1339 -2.1030 1.0156 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1540 0.7019 0.5149 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8143 0.2026 1.6850 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3769 3.5304 0.0435 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7936 -0.4072 -1.0393 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4791 0.5812 -2.4020 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9731 -2.3648 -0.1310 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3496 -1.3015 1.0142 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8051 0.3006 2.3606 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8596 -1.2304 2.7754 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6937 -1.3991 -2.5038 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.5748 -2.1596 1.9929 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2214 -0.4548 2.3753 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8554 1.4876 0.1664 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9521 2.5618 -1.0262 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4067 1.8512 -1.2747 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6664 5.1007 -1.6872 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3534 -0.0777 -0.9903 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8021 -4.0696 -0.5241 H 0 0 0 0 0 0 0 0 0 0 0 0 9.3512 2.8889 1.1876 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9020 3.5743 -0.3972 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 5 7 1 0 7 8 1 0 8 9 2 0 7 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 13 15 1 0 15 16 1 0 16 17 1 0 17 18 2 0 17 19 1 0 17 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 24 27 1 0 27 28 1 0 28 29 2 0 29 30 1 0 30 31 2 0 31 32 1 0 32 33 2 0 33 34 1 0 34 35 2 0 31 36 1 0 22 37 1 0 37 38 1 0 38 39 1 0 39 40 2 0 39 41 1 0 39 42 1 0 12 43 1 0 11 44 1 0 3 45 1 0 6 1 1 0 9 4 1 0 14 10 1 0 25 21 1 0 35 27 1 0 35 30 1 0 1 46 1 0 8 47 1 0 10 48 1 0 11 49 1 0 12 50 1 0 13 51 1 0 15 52 1 0 15 53 1 0 19 54 1 0 21 55 1 0 22 56 1 0 24 57 1 0 25 58 1 0 26 59 1 0 28 60 1 0 33 61 1 0 36 62 1 0 36 63 1 0 37 64 1 0 37 65 1 0 41 66 1 0 42 67 1 0 43 68 1 0 44 69 1 0 45 70 1 0 45 71 1 0 M END

Standard InCHIKey	GTUJJVSZIHQLHA-XPWFQUROSA-N
Standard InCHI	InChI=1S/C20H26N10O13P2/c21-15-9-17(25-3-23-15)29(5-27-9)19-12(32)11(31)7(41-19)1-40-45(37,38)43-14-8(2-39-44(34,35)36)42-20(13(14)33)30-6-28-10-16(22)24-4-26-18(10)30/h3-8,11-14,19-20,31-33H,1-2H2,(H,37,38)(H2,21,23,25)(H2,22,24,26)(H2,34,35,36)/t7-,8-,11-,12-,13-,14-,19-,20-/m1/s1
SMILES	C1=NC(=C2C(=N1)N(C=N2)C3C(C(C(O3)COP(=O)(O)OC4C(OC(C4O)N5C=NC6=C(N=CN=C65)N)COP(=O)(O)O)O)O)N

Calculated Properties

Physi-Chem Properties

Molecular Weight:	676.12	Volume:	545.941 ? Van der Waals volume.
Dense:	1.238	LogP:	-2.886 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	-0.323 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.677 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	10.0	Rigid Bonds:	32.0
TPSA:	340.91 ? Topological Polar Surface Area.	H-Bond Acceptor:	23.0
H-Bond Donor:	10.0	Rings:	6.0
Heavy Atoms:	25.0

MedChem Properties

QED Drug-Likeness Score:	0.079	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.983	Fsp³:	0.5
MCE-18:	141.333 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	1
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.028	Fluc inhibitor:	0.004 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.016 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.332 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.499	Promiscuous compounds:	0.042

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.847	MDCK Permeability:	-5.493
Pgp-inhibitor:	0.0	Pgp-substrate:	0.0
PAMPA:	1.0 ? 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):	0.043
20% Bioavailability (F20%):	0.0	30% Bioavailability (F30%):	0.002
50% Bioavailability (F50%):	0.001

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.259
Plasma Protein Binding (PPB):	25.957%	Volume Distribution (VD):	-0.615
Fu:	56.639% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.993
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.0
BSEP inhibitor:	0.126

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.002	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.001
HLM stability:	0.186 ? 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):

1.902

Half-life (T1/2):

1.948

ADMET: Toxicity

hERG Blockers:	0.007	hERG Blockers (10um):	0.011
Human Hepatotoxicity (H-HT):	0.633	Drug-induced Liver Injury (DILI):	0.999
AMES Toxicity:	0.139	Rat Oral Acute Toxicity:	0.054
Maximum Recommended Daily Dose:	0.999	Skin Sensitization:	0.451
Carcinogencity:	0.887	Eye Corrosion:	0.0
Eye Irritation:	0.004	Respiratory Toxicity:	0.997
Drug-induced Neurotoxicity:	0.988	Ototoxicity:	0.958
Hematotoxicity:	0.104	Drug-induced Nephrotoxicity:	1.0
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.436
A549 Cytotoxicity:	0.002	Hek293 Cytotoxicity:	0.75
BCF:	-0.021 ? 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:	2.32 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	3.869 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.553 ? 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
NPO30193	Mycoplasma genitalium	Species	Mycoplasmataceae	Bacteria	n.a.	n.a.	n.a.	PMID[22817898]
NPO30193	Mycoplasma genitalium	Species	Mycoplasmataceae	Bacteria	n.a.	n.a.	n.a.	Database[COCONUT]

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

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

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 NPC323608 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	36493
0.1-0.2	13183
0.2-0.3	68
0.3-0.4	41
0.4-0.5	32
0.5-0.6	20
0.6-0.7	7
0.7-0.8	2
0.8-0.85	3
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8056	Intermediate Similarity	NPC302778
0.8056	Intermediate Similarity	NPC329404
0.8056	Intermediate Similarity	NPC212551
0.7838	Intermediate Similarity	NPC130586
0.7639	Intermediate Similarity	NPC185991
0.7639	Intermediate Similarity	NPC321814
0.7632	Intermediate Similarity	NPC174802
0.7532	Intermediate Similarity	NPC606410
0.7467	Intermediate Similarity	NPC324198
0.7467	Intermediate Similarity	NPC326529
0.7467	Intermediate Similarity	NPC319100
0.7432	Intermediate Similarity	NPC164952
0.7	Intermediate Similarity	NPC323091
0.6585	Remote Similarity	NPC316618
0.6486	Remote Similarity	NPC136349
0.6486	Remote Similarity	NPC219313
0.6173	Remote Similarity	NPC224076
0.6067	Remote Similarity	NPC326082
0.6026	Remote Similarity	NPC85689
0.6	Remote Similarity	NPC328479
0.5833	Remote Similarity	NPC324484
0.5714	Remote Similarity	NPC21461
0.5698	Remote Similarity	NPC161224
0.5698	Remote Similarity	NPC481375
0.5663	Remote Similarity	NPC324033
0.5647	Remote Similarity	NPC321458
0.561	Remote Similarity	NPC121222
0.56	Remote Similarity	NPC156461
0.56	Remote Similarity	NPC107374
0.56	Remote Similarity	NPC600382
0.56	Remote Similarity	NPC612067
0.5541	Remote Similarity	NPC317821
0.5534	Remote Similarity	NPC189261
0.5506	Remote Similarity	NPC484199
0.549	Remote Similarity	NPC90902
0.5481	Remote Similarity	NPC611055
0.5444	Remote Similarity	NPC484196
0.5432	Remote Similarity	NPC261595
0.506	Remote Similarity	NPC211025
0.5057	Remote Similarity	NPC195140

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC323608 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6679
0.1-0.2	2336
0.2-0.3	58
0.3-0.4	51
0.4-0.5	15
0.5-0.6	5
0.6-0.7	4
0.7-0.8	2
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
0.7639	Intermediate Similarity	NPD283	Phase 4
0.7632	Intermediate Similarity	NPD339	Phase 2
0.6486	Remote Similarity	NPD548	Clinical (unspecified phase)
0.6173	Remote Similarity	NPD169	Phase 2
0.6173	Remote Similarity	NPD338	Approved
0.6125	Remote Similarity	NPD4171	Clinical (unspecified phase)
0.5732	Remote Similarity	NPD242	Phase 4
0.56	Remote Similarity	NPD249	Phase 4
0.56	Remote Similarity	NPD250	Phase 4
0.549	Remote Similarity	NPD4716	Approved
0.5432	Remote Similarity	NPD247	Clinical (unspecified phase)

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